K-a? 
71 

R3 


PHYSIOLOGICAL  NOTES 


Randolph  and  Dixon 


UCrNRLF 


B    3    371    10H 


THE  LIBRARY 

OF 

THE  UNIVERSITY 
OF  CALIFORNIA 

PRESENTED  BY 

PROF.  CHARLES  A.  KOFOID  AND 
MRS.  PRUDENCE  W.  KOFOID 


NOTES 


FROM  THE 


PHYSIOLOGICAL  LABORATORY 


UNIVERSITY   OF   PENNSYLVANIA. 


EDITED    BY 

N.  *A.  RAXDQJLPH,  M.D., 

Assistant  Demonstrator  of  Physiology  in  the   University  of  Pennsylvania 
Fellow  of  the  College  of  Physicians  of  Philadelphia ;  Member  of  the 
American  Philosophical  Society,  of  the  Academy  of  Natural 
Sciences  of  Philadelphia,  of  the  Philadelphia  Neuro- 
logical Society,  of  the  Society  of  Naturalists 
of  the  Eastern  United  States,  and 
of  the  American  Society  for 
Psychical  Research, 


SAMUEL   G.  DIXOX, 

Assistant  Demonstrator  of  Physiology  at  the  University  of  Pennsylvania. 


PRINTED    BY 

J.   B.   LIPPIXCOTT    COMPANY, 

PHILADELPHIA. 

1885. 


B 


PREFACE. 


THE  papers  which  form  this  little  volume  are 
simply  the  brief  records  of  facts  of  interest  brought 
to  light  in  the  course  of  physiological  study. 

The  constant  aim  of  the  writers  has  been  to 
present  these  facts  with  the  greatest  conciseness 
compatible  with  scientific  accuracy. 

Judgment  upon  this  and  other  qualities  is,  how- 
ever, left  to  the  friendly  reader  by 

THE    EDITORS. 


M348932 


CONTENTS. 


PAGE 

I. — A  NOTE  ox  THE  F.ECES  OF  STARCH-FED  INFANTS. 
N.  A.  RANDOLPH.  Trans.  Col.  Phys.  Phila.,  3d  series, 
vol.  vi.,  1883 7 

II. — A^r  EXAMINATION  or  THE  FJECES  OF  TWENTY  PER- 
SONS RECEIVING  INUNCTIONS  OF  COD-LIVER  OIL. 
N.  A.  RANDOLPH  &  A.  E.  ROUSSEL.  Phila.  Med. 
Times,  1883 11 

III. — A  STUDY  OF  THE  DISTRIBUTION  OF  GLUTEN 
WITHIN  THE  WHEAT-GRAIN.  N.  A.  RANDOLPH. 
Proc.  Acnd.  Nat.  Sci.,  1883 16 

IV.— ON  CERTAIN  UNTOWARD  EFFECTS  OF  THE  ADMIN- 
ISTRATION OF  TURPETH  MINERAL.  N.  A.  RAN- 
DOLPH &  A.  E.  ROUSSEL.  Phila.  Med.  News,  1884  .  24 

V. — A  PRELIMINARY  NOTE  ON  A  REACTION  COMMON 
TO  PEPTONE  AND  BILE-SALTS.  N.  A.  RANDOLPH. 
Proc.  Acad.  Nat.  Sci.,  1884 31 

VI. — A  NOTE  ON  THE  BEHAVIOR  OF  HYDROBROMIC 
ACID  AND  OF  POTASSIUM  IODIDE  IN  THE  DIGEST- 
IVE TRACT.  N.  A.  RANDOLPH.  Read  before  the 
Phila.  Neurological  Society,  April  28,  1884  .  .  34 

VII. — ON  THE  DIGESTION  OF  RAW  AND  OF  BOILED 
MILK.  N.  A.  RANDOLPH  &  A.  E.  ROUSSEL.  Proc. 

Acad.  Nat.  Sci.,  1884 42 

1*  5 


6  Contents. 

PAGE 

VIII. — A  STUDY  or  THE  NUTRITIVE  VALUE  OF  BRANNY 
FOODS.  N.  A.  KANDOLPH  &  A.  E.  ROUSSEL.  Trans. 
Col.  Phys.  Phila.,  3d  series,  vol.  vii.,  1884  .  •  .44 

IX. — A  METASTATIC  HEAT  REGULATOR.  N.  A.  RAN- 
DOLPH. Journal  of  the  Franklin  Institute,  1884  .  69 

X. — ON  THE  BEHAVIOR  OF  PETROLATUM  IN  THE  DIGEST- 
IVE TRACT.  N.  A.  RANDOLPH.  Proc.  Acad.  Nat. 
Set.,  1884 73 

XI. — CUTANEOUS  ABSORPTION  OF  NICOTINE.  N.  A. 
RANDOLPH  &  SAMUEL  G.  DIXON.  Proc.  Acad. 
Nat.  Sci.j  1884  .  .  '.  " 76 

XII. — ON  THE  DIETETIC  FACTOR  IN  THE  TREATMENT 
OF  ANGINA  PECTORIS.  N.  A.  RANDOLPH.  Read 
before  P/tila.  Neurological  Soc.,  1884  .  .  .78 

XIII. — A  PAINLESS  ES'CHAROTIC.  N.  A.  RANDOLPH 

&  SAMUEL  G.  DIXON.  Phila.  Medical  News,  1885  81 

XIV. — ON  THE  CUTANEOUS  ABSORPTION  OF  SALICYLIC 
ACID.  N.  A.  RANDOLPH  &  SAMUEL  G.  DIXON. 
Phila.  Medical  News,  1885  .  .  .  .  .83 


I. 


A  NOTE  ON   THE   FJECES   OF  STARCH-FED 
INFANTS. 

THE  series  of  experiments  presented  in  the  pre- 
ceding paper  by  Dr.  Keating  seems  to  me  to  be  in 
the  highest  degree  suggestive,  for  it  is  only  rational 
to  suppose  that  the  development  of  the  amylolitic 
ferment  of  the  pancreatic  juice  is  coincident  with 
the  appearance  of  the  analogous  salivary  ferment.1 
Inasmuch,  however,  as  the  food  even  in  spoon-fed 
infants  is  retained  but  a  short  time  in  the  mouth, 
and  further,  as  the  continued  action  of  the  saliva 
after  it  enters  the  stomach  is  as  yet  problematical, 
the  only  absolute  control  for  such  observations  is 
afforded  by  an  examination  of  the  faeces. 

Through  the  kindness  of  Dr.  Keating  I  have 
been  enabled  to  examine  the  stools  of  twenty-four 
starch-fed  infants,  of  ages  varying  from  forty-five 
days  to  eighteen  months.  Twenty-three  of  these 
children  were  fed  upon  cracker-dust,  water,  and 

1  The  experiments  in  question  demonstrated  the  activity 
of  the  saliva  of  very  young  infants. 

7 


8        Notes  from  the  Physiological  Laboratory 

condensed  milk.  The  twenty-fourth  received  corn- 
starch  boiled  in  milk. 

The  freshly  evacuated  faeces  of  each  infant  were 
carefully  bottled  and  labelled,  and  a  drop  of  a  solu- 
tion of  iodine  was  added  to  a  small  portion  of  each 
specimen,  which  was  then  submitted  to  microscopi- 
cal examination.  Besides  turning  the  starch  blue, 
and  indicating  the  presence  of  dextrine  by  a  pecu- 
liar mahogany-red  color,  the  iodine  has  the  advan- 
tage of  rendering  any  fats  which  may  be  present 
much  more  readily  apparent.  The  reaction  of  each 
specimen  was  taken,  but  though  this  varied  from 
acid  to  alkaline  and  neutral,  no  correlation  between 
the  reactions  and  the  other  properties  of  the  speci- 
mens could  be  observed.  A  decoction  of  each  was 
tested  for  glucose  with  freshly-prepared  Feh ling's 
solution,  but  except  in  one  instance  no  appreciable 
amount  could  be  found. 

The  presence  of  starch  was  exceptional  and  ap- 
parently in  no  degree  dependent  upon  the  age  of 
the  child.  The  stools  of  eighteen  out  of  the 
twenty-four  children  contained  either  no  starch,  or 
but  a  trace, — i.e.,  no  more  than  is  frequent  in  the 
evacuations  of  a  healthy  adult  upon  a  mixed  diet. 
Six  of  these  specimens  were  from  children  of  three 
months  or  less, — the  youngest  being  but  forty-five 


of  the   University  of  Pennsylvania.  9 

days  old.  In  many  cases  the  broken  and  empty 
cellulose  envelopes  of  the  starch-granules  were 
clearly  discernible. 

The  six  infants  in  whose  evacuations  a  note- 
worthy amount  of  starch  was  present  were  aged 
respectively  three,  four,  ten,  thirteen,  fourteen,  and 
seventeen  months.  The  eldest  two  were  in  very 
bad  health. 

The  following  is  a  tabular  statement  of  the  age, 
diet,  and  appearances  of  the  faeces  in  the  children 
forming  the  subject  of  this  study : 

AN  EXAMINATION  OP  THE  F^CES  OF  TWENTY-FOUR  STARCH- 
FED   INFANTS. 


No. 

Name. 

Age. 

Food. 

Starch 
present. 

Remarks. 

1 

Savin  

45  days. 

Condensed 

None. 

milk  and 

cracker- 

dust. 

2 

Jocker  

2  mos. 

M 

Traces. 

3 

McGcttinger. 

2+  " 

•1 

** 

4 

McGowaii  

3      " 

» 

« 

Twice  examined  :  no 

fat    before    inunc- 

tion, about  10  per 

cent,  after. 

5 

ROSS  

3      " 

« 

« 

6 

Hays  

3      " 

" 

About  J4 

starch. 

7 

Sov  

3      " 

« 

Traces. 

8 

Ueuwich  

4      " 

Corn-starch 

« 

and  milk. 

9 

Moore  

4     " 

Condensed 

None. 

Many  broken  cellu- 

milk and 

lose  envelopes. 

cracker- 

dust. 

10 

Conway  

4+" 

Traces. 

Evidences  of  potato 

surreptitiously 

given. 

11 

Roach 

5      u 

<i 

About  % 

starch. 

12 

Anxier  

5+" 

'< 

None. 

13 

Schmiiz  

5+" 

« 

Many  bacteria. 

14 

McKinley  

(5+" 

" 

u 

10  per  cent,  fat;  had 

had  inunctions. 

10     Notes  from  the  Physiological  Laboratory 


AN  EXAMINATION  OF  THE  FAECES— (Continued). 


No. 

Name. 

Age. 

Food. 

Starch 
present. 

Remarks. 

15 

Hall 

8-f-  mos 

Breast  and 

Traces 

16 

17 

Hensen  
Devine  

10+" 
13—" 

cracker- 
food. 
Condensed 
milk  and 
cracker- 
dust. 
<( 

More  than 
normal. 

20  to   30 

Many  bacteria;   evi- 
dences   of     potato 
surreptitiously 
given. 
Some    glucose    pres- 

18 

Croncia  

14—" 

(i 

per  ct. 
Traces. 

ent  and  indications 
of  dextrine  ;  saliva 
was  found  to  be  iu- 
efficieut. 

19 

20 

Madden  
Boyle  

14     " 
14     " 

" 

10  per  ct. 

Sick. 

21 

22 
23 

24 

Glass  .... 

Kinscher  
Wood  

Dane  

14+" 

17—" 
17-" 

18      " 

M 

starch. 
None. 

Over     % 
starch. 

Traces. 

Except  a  few  large 
cells       containing 
starch  from  potato. 

Syphilitic;  saliva  was 
found  to  be  ineffi- 
cient. 
Indications    of   dex- 
trine. 

The  facts  presented  appear  to  justify  the  follow- 
ing conclusions : 

First,  that  many  infants  of  under  three  months 
can  digest  starchy  foods ; 

Second,  that  the  individual  variations  in  this  re- 
gard are  so  numerous  that  no  broad  and  general 
statement  can  be  made  as  to  the  period  at  which 
infants  begin  to  digest  starches;  and, 

Third,  that  the  physician  can  be  absolutely  cer- 
tain that  a  farinaceous  ingredient  in  the  diet  of  a 
young  infant  is  beneficial  only  by  an  examination 
of  the  dejecta  under  such  diet. 


of  the   University  of  Pennsylvania.  11 


ii. 


AN  EXAMINATION  OF  THE  FAECES  OF 
TWENTY  PERSONS  RECEIVING  INUNC- 
TIONS OF  COD-LIVER  OIL. 

IN  a  study  of  the  fseces  of  starch-fed  infants1  one 
of  us  observed  a  specimen  in  which  there  was  present 
a  very  notable  amount  of  oil-globules.  Upon  in- 
quiry, it  was  found  that  the  child  in  question  had 
been  receiving  inunctions  of  cod-liver  oil. 

The  same  coincidence  was  a  second  time  noted, 
and  the  following  series  of  experiments  was  then 
instituted. 

The  faeces  of  fourteen  infants,  in  fairly  average 
health,  were  examined  with  negative  results  as  far 
as  oil  was  concerned,  except  in  one  case. 

These  infants  were  then  thoroughly  rubbed  with 
cod-liver  oil  twice  daily  for  eleven  days,  care  being 
taken  to  cleanse  the  surface  of  the  body  after  each 

1  Randolph :  Transactions  of  the  College  of  Physicians  of 
Philadelphia,  3d  series,  vol.  vi.  p.  443. 


12     Notes  from  the  Physiological  Laboratory 

inunction,  and  the  faeces  of  each  examined  for  oil  at 
the  end  of  the  third  and  of  the  eleventh  day  of 
inunction.  At  the  end  of  the  third  day,  traces  of 
fat  were  observed  in  the  majority  of  the  specimens. 
On  the  eleventh  day  all  but  three  specimens  ex- 
hibited, on  microscopical  examination,  a  decidedly 
notable  quantity  of  unabsorbed  fat, — numerous  oil- 
globules  being  apparent  in  every  field. 

In  like  manner  an  examination  was  made  of  the 
dejecta  of  six  adults,  after  which  each  was  twice 
daily  well  rubbed  with  cod-liver  oil  in  the  groins 
and  axillae  for  a  period  of  three  weeks.  The  faeces 
of  the  adults  contained  normally  much  more  fat 
than  those  of  the  infants,  but  in  all  but  one  case 
there  was  a  well-marked  increase  in  the  proportion 
of  fatty  globules  at  the  end  of  the  treatment. 

The  circumstances  of  the  examination  precluded 
the  application  of  the  ether  method  for  the  estima- 
tion of  fats,  and  we  were  forced  to  rely  upon  a  close 
microscopical  examination.  For  the  micrometric 
method  only  relative  accuracy  is  claimed,  and  we 
hope  soon  to  be  able  to  go  over  the  same  ground, 
substituting  a  chemical  for  the  optical  method  in 
the  determination  of  fats.  By  the  use,  however,  of 
well-mixed  specimens,  and  by  carefully  averaging 
the  contents  of  many  fields  from  the  same  specimen, 


of  the  University  of  Pennsylvania. 


13 


we  have  obtained  results  which  we  believe  accu- 
rately represent  the  changes  in  the  relative  propor- 
tion of  fat  in  the  specimens  examined,  although  the 
unit  assumed  may  not  correspond  with  that  obtained 
by  gravimetric  methods. 

The  individuals  under  observation  were  upon  a 
diet  practically  uniform  in  composition  and  quan- 
tity, both  before  and  during  the  treatment.  At  the 
end  of  the  period  of  inunction  a  marked  gain  in 
weight  and  general  health  was  noted  in  the  majority 
of  the  cases. 

The  results  of  our  study  are  indicated  in  the  fol- 
lowing tables : 


ga 

ga 

SJj 

S*"1  _• 

.a1"1   • 

o        • 

No. 

Age. 

Diet. 

C  ^  *3 

H'»-2 

«•„! 

fc  ^U 

^  >.  "S 

2*§ 

S  9  a 

§5* 

<M  s 

1 

2  months. 

Milk  and  crackers. 

Negative. 

Negative. 

Negative. 

2 
3 

3 

((                                     (C 

!! 

Traces. 

3    per  cent. 
3.5  "      " 

4 

5 

Corn-starch  and  milk. 

" 

5      "     " 

5 

5 

Milk  and  crackers. 

M 

«• 

3      "     " 

6 

7 

5 

6 

«                   « 

Traces. 

Negative. 
Traces. 

Negative. 
Traces. 

8 
9 

6 

8 

«                   « 

Negative. 

Negative. 

" 

3.5  per  cent. 
5      "      " 

10 

11 

(i                   ii 

« 

Traces. 

3.5  "      " 

11 

12 

« 

3      **      ** 

12 

14 

«<                   « 

«« 

« 

3.5  "      " 

13 

14        « 

" 

« 

H 

2.5   "     " 

14 

15        " 

Corn-starch  and  milk. 

" 

(1 

3.5   «•     " 

14     Notes  from  the  Physiological  Laboratory 


No. 

Age. 

Diet. 

Fat  in  Faeces 
before  Inunc- 
tion. 

Fat  in  Faeces 
after  21  Days' 
Inunction. 

1  

Adult 

Hospital  Diet 

Traces 

Traces. 

2 

:{  

it 

«            <( 

2    "      " 

10+    "      " 

4. 

(4 

<(           M 

3    "       " 

10       "      " 

5 

4i 

((                      1C 

G  

K 

«           (1 

It  will  be  seen,  from  the  tables  given  above,  that 
in  80  per  cent,  of  the  cases  a  notable  increase  of  the 
fatty  matters  passed  per  an  urn  was  observed  after  the 
persistent  inunction  of  cod-liver  oil.  In  the  remain- 
ing 20  per  cent,  the  quantity  of  faecal  fats  was  un- 
altered by  the  treatment,  and  in  one  case  remained 
negative  throughout. 

We  venture  to  suggest,  as  a  provisional  hypothe- 
sis, that  by  the  continued  inunction  the  circulating 
fluids  became  to  some  extent  surcharged  with  fats, 
and  that,  in  consequence,  a  certain  amount  of  the 
fatty  constituents  of  the  food  was  refused  by  the  ab- 
sorbent surfaces  of  the  intestine  and  passed  from  the 
body  unaltered.  This  supposition  is  strengthened 
by  the  observations  of  Berthe,1  who  showed  that 
pure  cod-liver  oil,  given  internally,  could  be  taken 
for  a  longer  time  without  appearing  in  the  feeces, 


1  L'Union  Medicale,  t.  x.  No.  62,  1856. 


of  the  University  of  Pennsylvania.  15 

than  could  an  equal  amount  of  butter  or  any  of  the 
other  animal  and  vegetable  fats. 

We  further  suggest  that,  in  practice,  the  increase 
of  fat  in  the  stools  constitutes  a  physiological  test 
for  the  efficiency  of  the  aliptic  treatment  in  the  great 
majority  of  cases,  and  that  by  the  application  of  this 
test  both  the  frequency  of  exhibition  and  the  amount 
of  a  remedy  rather  repugnant  to  the  average  patient 
may  be  reduced  to  the  minimum  necessary  for  effi- 
cient treatment. 


16      Notes  from  the  Physiological  Laboratory 


in. 


A  STUDY  OF  THE  DISTRIBUTION  OF  GLUTEN 
WITHIN  THE  WHEAT-GRAIN. 

THE  object  of  the  present  paper  is  to  briefly  de- 
scribe several  methods  for  the  demonstration  of 
gluten  in  the  central  portion  of  the  wheat-grain,  and 
the  results  of  their  application. 

For  many  years  the  great  majority  of  observers 
and  of  writers  upon  gluten  have  stated  that  this 
highly  important  nitrogenous  element  of  food  is 
found  almost,  if  not  quite  exclusively,  in  the  fourtli 
layer  (Parkes)  of  the  grain,  immediately  below  and 
adherent  to  the  third  or  inner  coat  of  the  true  bran. 
This  fourth  layer  is  composed  of  closely-packed  yel- 
lowish granular  cells  of  ovate  or  cuboid  form,  each 
of  which  is  provided  with  a  dense,  laminated  cellu- 
lose wall,  and  contains  a  large  proportion  of  free  fat. 
Immediately  within  this  layer  of  so-called  "  gluten- 
cells,"  and  constituting  the  greater  portion  of  the 
grain,  is  an  aggregation  of  much  larger,  usually 
elongated,  cylindrical  cells,  whose  contents  are  appa- 


of  the   University  of  Pennsylvania.  17 

rently  made  up  exclusively  of  starch-granules  which 
exhibit  great  diversity  in  size. 

So  fixed  and  widespread  has  the  belief  become 
that  the  gluten  of  the  wheat  resides  in  specific  corti- 
cal cells  of  the  grain,  that  not  only  do  many  most 
intelligent  persons  habitually  rasp  their  digestive 
surfaces  with  branny  foods,  but  attempts  to  deter- 
mine, by  microscopical  examination,  the  nutritive 
values  of  various  prepared  foods  have  been  made, 
in  which  the  proportion  of  "  gluten-cells"  found  in 
a  given  food  formed  the  criterion  of  its  value.1 
These  assumptions  have  called  forth  merited  criti- 
cism from  Prof.  Richardson,  of  this  city,  and  from 
Prof.  Leeds,  of  Hoboken,  both  of  whom  empha- 
sized the  fact,  singularly  ignored  by  Cutter,  Jacobi, 
and  their  followers,  that  ordinary  white  wheat-flour 
contains  a  varying  but  always  notable  quantity  of 
gluten. 

So  far  as  the  writer  is  informed,  however,  there 
has  not  been  recorded  any  ocular  demonstration  of 
the  gluten  of  the  wheat-grain,  in  situ  and  entirely 
independent  of  the  "gluten-cells."  Such  a  demon- 
stration may  be  conclusively  made  by  either  of  the 
following  methods : 


1  E.  Cutter,  M.D.,  Galliard's  Mod.  Jour.,  Jan.  1882. 
2* 


18      Notes  from  the  Physiological  Laboratory 

1.  If  whole  wheat-grains  be  macerated  in  water 
to  which  a  few  drops  of  ether  have  been  added  to 
prevent  germination,  they  will,  in  a  few  days,  be- 
came thoroughly  softened,  and  the  contents  of  each' 
grain  may  then  be  squeezed  out  as  a  white  tena- 
cious mass.  Examination  of  the  remaining  bran 
shows  the  "gluten-cells"  undisturbed,  closely  adher- 
ing to  the  cortical  protective  layers.  By  now  care- 
fully washing  the  white  extruded  mass,  the  major 
part  of  its  starch  may  be  removed ;  and  upon  the 
addition  of  a  drop  of  iodine  solution,  microscopic 
examination  shows  numerous  net- works  of  fine  yel- 
low fibrils,  still  holding  entangled  in  the'ir  meshes 
many  starch-granules  colored  blue  by  the  iodine. 
In  carefully-washed  specimens,  these  sponge-like 
net-works  are  seen  to  retain  the  outline  of  the  cen- 
tral starch-filled  cells,  and  evidently  constitute  the 
protoplasmic  matrix  in  which  the  starch-granules 
lay.  Upon  gently  teasing  such  a  specimen  under  a 
moderate  amplification  the  fibrils  will  be  seen  to  be- 
come longer  and  thinner  in  a  manner  possible  only 
to  viscid  and  tenacious  substances, — a  class  repre- 
sented in  wheat  by  gluten  alone. 

An  eminently  satisfactory  proof  of  the  proteid 
nature  of  these  central  net-works  may  be  obtained  by 
heating  the  specimen  in  the  solution  of  acid  nitrate 


of  the   University  of  Pennsylvania.  19 

of  mercury  (Millon's  reagent),  when  the  fibrils  will 
assume  the  bright  pink  tint  characteristic  of  albu- 
minoids under  this  treatment.  The  results  of  the 
application  of  the  xanthoproteic  and  biuret  re- 
actions are  equally  conclusive,  but  .more  care  is  re- 
quired in  the  use  of  these  proteid  tests,  and  the 
resultant  differentiation  is  not  so  clear.  Reticuli 
similar  to  those  above  described,  but  much  broken 
and  smaller,  may  be  seen,  upon  close  examination, 
scattered  throughout  fine  white  flour,  without  the 
addition  of  any  reagent. 

By  general  consent,  the  albuminoids  of  the  wheat- 
grain  are  grouped  together  as  gluten,  which  is,  how- 
ever, further  separable  into  gluten-fibrin,  gliadin, 
and  mucedin,  proteid  bodies  practically  equal  in 
nutritive  value,  but  differing  in  certain  physical 
properties,  notably  that  of  solubility.  It  must, 
therefore,  be  borne  in  mind  that  in  this,  as  in  all 
other  methods  of  separating  gluten  from  the  other 
constituents  of  the  grain,  its  relatively  small  soluble 
portion  is  removed  with  the  starch,  and  that  any 
estimate  of  the  quantity  of  gluten  based  upon  such 
methods  will  probably  be  rather  under  than  over 
the  actual  amount. 

2.  In  even  the  thinnest  sections  of  the  wheat-grain, 
the  gluten  of  the  central  portion  is  always  masked 


20     Notes  from  ike  Physiological  Laboratory 

by  large  numbers  of  starch-granules.  These  may, 
to  a  large  extent,  be  removed  by  immersing  the  sec- 
tion for  a  short  time  in  liquor  potassse,  with  subse- 
quent careful  washing.  The  alkali  effects  the  hy- 
dration  and  partial  solution  of  the  starch ;  but  if  its 
application  be  too  long  continued,  the  gluten  will 
also  be  dissolved.  This  treatment  is  well  adapted  to 
show  the  rather  dense  gluten  net- works  usually  found 
in  bran,  immediately  below  the  fourth  layer. 

3.  The  most  satisfactory  method  of  studying  the 
distribution  of  gluten  in  sections  of  wheat  is  that  of 
artificial  salivary  digestion.  If  the  section  be  gently 
boiled  for  a  moment  to  hydrate  the  starch,  then 
transferred  when  cool  to  filtered  saliva,  and  main- 
tained for  from  half  an  hour  to  an  hour  at  a  tem- 
perature of  about  98°  Fahr.,  all  the  starch  will  be 
digested  away,  while  the  insoluble  proteid  and  other 
constituents  will  remain  entirely  unaltered.  A 
section  of  wheat-grain  thus  treated  will  exhibit, 
throughout  its  entire  central  portion,  close-meshed 
gluten  net-works,  which  become  slightly  denser  to- 
ward the  cortex  of  the  grain.  The  proteid  char- 
acter of  these  reticuli  is  here,  as  in  the  first  method, 
susceptible  of  micro-chemical  demonstration  by  Mil- 
Ion's  reagent  or  the  biuret  reaction.  A  relatively 
very  faint  coloration,  indicating  the  presence  of 


of  the   University  of  Pennsylvania.  21 

albuminoids,  is  noticeable  in  the  "  gluten-cells," 
while  the  gradual  condensation  of  the  gluten  of  the 
endosperm  as  the  cortex  is  approached,  is  evidenced 
by  a  quite  vivid  coloration  of  the  fibrils. 

Schenk  *  has  applied  Millon's  reagent  to  sections 
of  wheat  with  a  resultant  assumption  by  the  endo- 
sperm of  a  pink  tint  and  "  no  coloration  of  the  corti- 
cal gluten-cells."  The  starch  was  not  removed,  and 
the  method  of  distribution  of  gluten  was  not  deter- 
mined. By  artificial  gastric  digestion  of  wheat  sec- 
tions, the  same  observer  noted  that  the  starch  of  the 
section  became  readily  detached,  and  deduced  from 
this  the  just  proposition  that  the  gluten  lay  between 
the  starch-granules. 

Objections  are  not  infrequently  offered  by  the 
chemist  to  the  microscopical  determination  of  or- 
ganic compounds,  especially  where  any  attempt  at  a 
quantitative  estimation  is  made.  All  that  is  claimed 
for  the  methods  above  described  is  the  demonstration 
of  gluten  in  very  considerable  quantity  in  the  inner 
layers  of  the  wheat-grain.  It  is  but  just  to  state, 
however,  that  by  these  methods  a  conception  may 
be  obtained  of  the  quantity  of  proteids  within  the 
grain  fully  as  accurate  as  that  given  by  the  usual 

1  Anat.-Physiol.-Unters.,  p.  32.     Wien,  1872. 


22     Notes  from  the  Physiological  Laboratory 

chemical  method  of  estimating  the  albuminoids  of 
a  given  body,  namely,  from  the  entire  amount  of 
nitrogen  contained  in  it.  Especially  is  this  true  in 
the  case  of  vegetable  tissues.  In  a  close  analysis  of 
the  potato,  Schultze  and  Barbieri  found  that  only 
56.2  per  cent,  of  all  its  nitrogen  existed  in  albu- 
minoid combination,  while  in  the  fodder-beet  only 
20  per  cent,  of  the  nitrogen  went  to  the  formation 
of  albuminous  compounds;  the  remainder  in  each 
case  entering  into  the  composition  of  non-nutritious 
bodies,  as  amides,  nitrates,  ammonia,  and  asparagin. 

The  fact  that  the  gluten  net- works  become  denser 
toward  the  periphery  of  the  endosperm,  together 
with  the  presence  of  non-albuminoid  nitrogenous 
compounds  in  the  perisperm,  explains  the  notable 
percentage  of  nitrogen  found  in  bran  as  ordinarily 
roughly  removed. 

The  color-tests  mentioned  above  indicate  that  the 
amount  of  proteids  contained  in  the  cells  of  the 
fourth  layer  is  relatively  very  slight;  but  admitting 
for  the  moment  that  these  cells  contain  gluten, 
the  question  naturally  arises  whether,  in  view  of 
their  dense  cellulose  walls,  they  are  capable  of  serv- 
ing as  a  food-stuff  for  man.  In  artificial  digestion 
the  writer  has  found  these  elements,  even  when 
thoroughly  cooked,  to  be  unaffected  by  the  digestive 


of  the   University  of  Pennsylvania.  23 

juices ;  that  is,  well-boiled  bran  with  its  adherent 
"gluten-cells/'  will  sustain  prolonged  maceration  at 
the  temperature  of  the  human  digestive  tract  in 
artificial  gastric  and  pancreatic  juice  (in  which, 
under  the  same  conditions,  fibrin  is  readily  digested) 
without  exhibiting  any  change.  These  cells  were 
further  found  to  be  unaffected  by  maceration  for 
thirty  days  in  liquor  potassse,  except  for  a  slight 
swelling  of  the  cell  and  the  occasional  coalescence  of 
some  of  its  contained  oil-globules.  They  were  also 
practically  unchanged  by  a  few  days'  immersion  in 
strong  nitric  acid.  In  order  to  obtain  conclusive  and 
unassailable  results  as  to  the  nutritive  value  of  the 
"  gluten-cells"  as  far  as  man  is  concerned,  the  writer 
has  at  present  under  observation  a  number  of  healthy 
adults,  who  daily  receive,  in  addition  to  their  regu- 
lar diet,  a  small  fixed  amount  of  boiled  bran.  Their 
alvine  dejections  (containing  all  the  undigested  ele- 
ments of  food  after  the  normal  action  of  all  the 
digestive  juices)  will  be  submitted  to  close  micro- 
scopical examination,  with  a  view  to  ascertaining 
the  extent  to  which  the  "gluten-cells"  have  been 
digested,  and  a  report  will  be  made  upon  the  results 
in  the  near  future. 


24     Notes  from  the  Physiological  Laboratory 


ON   CERTAIN  UNTOWARD  EFFECTS  OF  THE 
ADMINISTRATION  OF  TURPETH  MINERAL. 


have  recently  had  under  our  personal  ob- 
servation five  cases  in  which  the  administration  of 
turpeth  mineral  was  followed  by  unexpected  symp- 
toms. 

On  the  occasion  in  question  each  of  eight  well- 
nourished  men,  in  average  health,  was  given  five 
grains  of  turpeth  mineral  ;  *  and  as  emesis  did  not 
follow  within  half  an  hour,  three  grains  additional 
were  given,  with  the  result  of  inducing  vomiting, 
more  or  less  copious,  within  twenty  minutes  after 
the  administration  of  the  second  dose.  Beyond  a 
continuation  of  the  retching  for  some  time  and  a 
general  complaint  of  a  sense  of  burning  in  the 
throat  and  fauces,  nothing  unusual  was  observed  at 
the  time,  and  but  little  depression  immediately  fol- 
lowed the  emesis. 

1  The  drug  was  purchased  from  a  reliable  wholesale  dealer 
in  this  city. 


of  the   University  of  Pennsylvania.  25 

On  the  following  morning,  however,  our  atten- 
tion was  called  to  the  condition  of  five  out  of  the 
eight  men  above  mentioned.  A  rather  violent  diar- 
rhoea had  followed  in  from  ten  to  twenty  hours 
after  the  administration  of  the  drug,  attended  by 
much  griping  and  a  rather  unusual  amount  of  con- 
stitutional depression.  Each  of  these  five  men.  had 
passed  in  the  twenty-four  hours  succeeding  the  ex- 
hibition of  the  drug  from  eight  to  fifteen  stools. 
These  stools  at  first  resembled  those  of  calomel,  but 
eventually  became  yellow.  Appropriate  treatment 
was  administered,  and  on  the  following  day  the 
diarrhoea  was  partially  or  wholly  checked,  and  the 
cases  progressed  favorably  to  recovery.  It  is  worthy 
of  note  that  in  each  case  the  first  few  stools  con- 
tained minute  particles  of  the  yellow  sulphate, 
showing  that  not  only  had  its  elimination  by  emesis 
been  far  from  complete,  but  also  that  the  drug  had 
been  for  from  ten  to  twenty  hours  in  contact  with 
the  tissues  and  fluids  of  the  digestive  tract. 

In  the  fifth  case,  John  H.,  a  German,  set.  38, 
complained  of  a  soreness  of  his  gums,  and  of  the 
large  amount  of  saliva  dribbling  from  his  mouth. 
He  had  up  to  this  time  received  no  preparation  of 
mercury  for  several  months.  An  examination 
showed  the  gums  to  be  soft  and  spongy,  with  the 


26      Notes  from  the  Physiological  Laboratory 

teeth  partially  loosened,  the  tongue  swollen,  cov- 
ered with  a  thick,  yellowish  coat,  and  showing  dis- 
tinctly the  imprint  of  each  tooth.  This,  together 
with  the  large  amount  of  saliva  secreted,  and  the 
characteristic  fetor  of  the  breath,  proved  it  to  be  a 
well-marked  case  of  salivation,  such  as  is  for- 
tunately rarely  witnessed  at  the  present  day,  either 
in  hospital  or  general  practice.  Under  appropriate 
treatment,  however,  the  man  improved,  and  was 
ultimately  cured. 

Had  the  cases  been  younger  or  less  vigorous,  a 
different  termination  might  have  resulted. 

At  the  time  we  regarded  these  results  as  peculiar, 
but  shortly  afterwards  our  attention  was  called  to 
an  article  by  Dr.  McPhedran,1  in  which  was  given 
a  detailed  account  of  two  fatal  cases  occurring  in 
children,  in  which,  however,  emesis  failed  to  result, 
as  also  a  similar  case  in  the  Medical  and  Surgical 
Reporter.2 

Upon  examining  the  literature  of  the  subject  we 
find  that  Dr.  Hubbard,  of  Maine,  was  among  the 
first  to  use  this  drug;  but  to  Dr.  Fordyee  Barker, 
of  New  York,  belongs  the  credit  of  bringing  it 

1  The  Medical  News,  December  22,  1883,  p.  682. 

2  January  19,  1884,  p.  93. 


of  the   University  of  Pennsylvania.  27 

prominently  before  the  attention  of  the  profession. 
In  an  article  on  "  Croup," l  Dr.  Barker  states  that 
after  an  experience  of  twenty  years  he  considers 
turpeth  mineral  the  best  emetic  for  use  in  this  dis- 
ease, and  goes  so  far  as  to  recommend  that  it  be 
kept  on  hand  in  all  families  with  children  of  a 
croupy  tendency,  administered  at  the  earliest  symp- 
toms of  an  attack,  and  before  sending  for  a  phy- 
sician. 

Abroad,  also,  the  drug  seems  to  have  been  re- 
ceived with  favor.  Drs.  Desmartis  and  de  Titray,2 
who  consider  the  membrane  in  croup  as  due  to  the 
result  of  blood-poisoning  of  a  fermentative  charac- 
ter, advocate  the  merits  of  the  remedy  as  twofold, 
viz.,  as  exerting  a  specific  agency  upon  the  ferment, 
and  also  as  removing  the  deposits  by  emesis.  They 
record  its  use  in  a  number  of  cases  of  different  ages 
with  good  results. 

Again,  Dr.  Smith,3  in  his  work  on  "  Diseases  of 
Children,'7  speaks  of  this  drug  in  connection  with 
croup,  and  mentions  it  as  probably  the  'best  emetic 
in  ordinary  cases  of  this  disease. 


1  American  Journal  of  Obstetrics,  May,  1870. 

2  Nouveau  Traiternent  du  Croup,  etc.,  Paris,  1860,  p.  28. 

3  Fifth  edition,  p.  548. 


28      Notes  from  the  Physiological  Laboratory 

Prof.  Alfred  Stille*1  quotes  two  cases  occurring  in 
adults  with  fatal  results.  In  one,  a  boy,  aged  six- 
teen, took  about  a  drachm  of  this  drug;  symptoms 
of  the  ingestion  of  an  irritant  poison  followed,  to- 
gether with  great  salivation,  and  death  ensued  in  a 
week's  time.2 

"In  the  second  case,  a  man,  set.  27,  took  forty 
grains  of  this  medicine  by  mistake  for  JEthiops 
mineral.  The  primary  symptoms  were  precisely 
the  same  as  in  the  above  case  just  related.  Death 
occurred  at  the  end  of  ten  days.  The  inner  surface 
of  the  month,  gums,  palate,  and  fauces  were  cov- 
ered with  black  sloughs ;  the  parotid  and  submax- 
illary  glands  were  enlarged ;  the  mucous  membrane 
throughout  the  intestinal  canal  was  softened  and 
easily  torn ;  the  glands  of  the  stomach  and  intes- 
tines unnaturally  large;  the  kidneys  were  much 
enlarged,  and  the  bladder  full  of  urine."  3 

A  case  of  poisoning,  with  recovery,  by  the  same 
drug,  in  a  dose  of  "less  than  a  drachm,"  is  reported 
by  Yowndes.4 


1  Therapeutics,  fourth  edition,  vol.  ii.  p.  769. 

2  Letheby,  London  Medical  Gazette,  xxxix.  p,  474. 

3  Taylor,  Guy's  Hospital  "Reports,  3d  series,  x.  180. 

4  Abstract  in  Lancet,  March  10,  1860. 


of  the   University  of  Pennsylvania.  29 

In  the  "United  States  Dispensatory"1  we  find 
it  stated  that  the  drug  in  question  operates  with 
great  promptitude,  but  sometimes  excites  saliva- 
tion. 

As  seen  by  the  references  above  given,  our  cases 
present  little  of  novelty,  excepting  that  the  dose  we 
used  was  quite  within  therapeutic  limits  as  ordi- 
narily given  ;  but  we  deem  it  our  duty  to  call  atten- 
tion to  the  danger  attending  the  administration  of 
this  drug,  especially  as  its  poisonous  properties 
seem  to  have  been  overlooked  by  several  recent 
writers  on  therapeutics. 

Prof.  Bartholow,2  it  is  true,  states  that  "  serious 
results  might  be  produced  if  emesis  did  not  so 
promptly  follow,"  which  seems  to  agree  with  the 
experience  of  Dr.  McPhedran,  already  mentioned. 
In  the  cases  under  our  own  observation,  however, 
the  poisonous  symptoms  followed,  notwithstanding 
that  fairly  copious  emesis  resulted  in  every  case. 
The  time  which  elapsed  between  exhibition  and 
emesis  (thirty-five  to  fifty  minutes)  was  possibly 
sufficient  to  permit  the  occurrence  of  chemical 
changes  in  the  drug  as  it  lay  in  the  stomach,  and 


1  Fifteenth  edition,  p.  767. 

2  Therapeutics,  fifth  edition,  p.  252. 

3* 


30      Notes  from  the  Physiological  Laboratory 

the  minimum  time  of  ten  hours  elapsing  between 
the  ingestion  of  the  drug  and  its  final  elimination 
with  the  faeces  was  (in  one  case  at  least)  fully  suf- 
ficient to  account  for  the  resultant  symptoms,  which 
were  of  a  character  tending  to  substantiate  the 
statement  of  Miahle,  that  all  mercurial  preparations 
are  absorbed  in  the  form  of  chlorides.1 

We  are  informed  by  several  prominent  dealers  in 
drugs  that  the  demand  for  turpeth  mineral  is  quite 
large,  and  is  apparently  growing.  This  fact,  to- 
gether with  the  praise  it  has  received  in  several 
quarters,  justifies  us  in  emphasizing  the  following 
conclusions,  based  upon  the  observations,  old  and 
new,  which  are  given  above : 

1.  That  a  dangerous  quantity  of  turpeth  mineral 
often  remains  in  the  stomach  after  emesis. 

2.  That  this  drug  possesses  sufficient  toxic  and 
irritant  properties  not  only  to  demand   from   the 
profession   much,   more   than   usual   caution   in   its 
administration,  but  to  condemn  its  use  where  the 
exhibition  of  any  other  emetic  is  practicable. 

3.  That  it  should  not  be  placed  in  the  hands  of 
1  te  laity. 

1  See  the  Medical  News,  January  26,  1884,  p.  89. 


of  the   University  of  Pennsylvania.  31 


A  PRELIMINARY  NOTE  ON  A  REACTION  COM- 
MON TO  PEPTONE  AND  BILE-SALTS. 

IF  the  acid  nitrate  of  mercury  (Millon's  reagent) 
be  added  to  a  cold  aqueous  solution  of  potassium 
iodide,  a  red  precipitate  of  mercuric  iodide  always 
appears.  When,  however,  either  peptone  or  biliary 
salts  are  present  in  noteworthy  amount,  the  precipi- 
tate of  nascent  mercuric  iodide  assumes  the  yellow 
phase.  As  practically  applied,  the  red  may  vary 
from  salmon  to  scarlet,  the  yellow  from  pale  lemon 
to  orange. 

In  order  to  render  the  test  sensitive  to  the 
presence  of  minute  quantities  of  the  substances 
in  question,  it  is  necessary  to  limit  the  amount 
of  potassium  iodide  employed.  Thus  to  each  five 
cubic  centimetres  of  the  suspected  fluid — which 
must  be  cold  and  either  neutral  or  faintly  acid — are 
added  two  drops  of  a  saturated  solution  of  potas- 
sium iodide,  the  two  liquids  being  well  mixed. 


32      Notes  from  the  Physiological  Laboratory 

Four  or  five  drops  of  Millon's  reagent  are  now 
added,  the  contents  of  the  vessel  thoroughly  stirred 
or  shaken.  Under  these  circumstances  the  presence 
of  peptone  in  amounts  of  less  than  one  part  in  five 
thousand  is  readily  shown.  By  reducing  the  quan- 
tities of  the  reagents  used  it  is  possible  to  demon- 
strate the  presence  of  peptone  in  a  solution  con- 
taining but  one  part  of  that  body  in  seventeen 
thousand  parts  of  water. 

The  conditions  interfering  with  this  reaction  are : 
alkalinity  of  the  fluid  examined  (readily  overcome 
by  neutralization) ;  heat,  which  has  the  same  influ- 
ence upon  the  nascent  mercuric  iodide  as  have  pep- 
tone and  the  bile-salts;  and  the  presence  of  certain 
compounds,  as  potassium  ferrocyanide,  which  chem- 
ically prevent  the  production  of  the  mercuric 
iodide. 

The  following  bodies  in  moderate  amount  do  not 
affect  the  reaction :  saliva,  syntonin,  amygdalin, 
para-albumen,  diastase,  kreatin,  leucin,  tyrosin, 
mucic  acid,  glucose,  urea,  uric  acid,  nitric,  hydro- 
chloric, sulphuric,  and  picric  acids,  glycerine,  alco- 
hol, atropia  sulphate,  pilocarpin  nitrate,  caffeine, 
sodium  carbonate,  ammonium  oxalate,  sodium 
phosphate,  and  manganese  chloride  and  ferric 
chloride. 


of  the   University  of  Pennsylvania.  33 

[This  test  is  not  applicable  to  urine,  nor  is  it 
available  in  the  presence  of  albumen  or  gelatin.] 

It  is  obvious  that  this  reaction  is  useless  to  the 
student  as  an  isolated  test,  inasmuch  as  it  responds 
to  two  entirely  distinct  compounds,  but  its  sim- 
plicity and  striking  colorations  give  it  very  consid- 
erable value  when  employed  in  corroboration  of 
other  tests. 


34      Notes  from  the  Physiological  Laboratory 


A  NOTE  ON  THE  BEHAVIOR  OF  HYDROBRO- 
MIC  ACID  AND  OF  POTASSIUM  IODIDE  IN 
THE  DIGESTIVE  TRACT.1 

I  VENTURE  to  present  before  the  Society  a  brief 
note  upon  a  subject  not  strictly  neurological,  but 
having  direct  bearing  upon  the  relations  entertained 
to  the  processes  of  digestion  by  two  drugs,  which 
are  of  interest  to  the  neurologist. 

In  a  series  of  artificial  digestions,  in  which  hy- 
drobromic  acid  was  present  in  the  digestive  mixture 
in  amount  corresponding  to  the  therapeutic  dose,  I 
have  noted, — 

(a)  That  salivary  digestion  was  completely  sus- 
pended, whereas 

(6)  The  peptonization  of  proteid  food-stuffs  was 

1  The  general  deductions  herein  made  from  the  study  of 
these  two  drugs  are  applicable  respectively  to  all  acid  and 
alkaline  drugs  given  by  the  mouth,  and  a  more  descriptive 
title  of  the  paper  would  have  been  "  Time  Relations  in  the 
Exhibition  of  Acids  and  of  Alkalies." 


of  the   University  of  Pennsylvania.  35 

in  no  wise  retarded,  the  variation  from  the  nor- 
mal, if  any,  being  toward  an  acceleration  of  this 
process. 

It  is  evident,  therefore,  that,  other  things  being 
equal,  the  appropriate  time  for  the  exhibition  of 
this  drug  is  immediately  upon  the  cessation  of  sali- 
vary digestion  within  the  stomach,  or,  in  other 
words,  upon  the  first  formation  of  free  acid  within 
that  viscus. 

Recent  studies1  have  shown  that  the  acidity  of 
the  gastric  contents,  found  even  in  quite  early  stages 
of  digestion,  is  not  due  to  the  presence  of  free  acid  ; 
and  the  ingenious  observations  of  Von  den  Velden2 
go  far  toward  proving  that  the  development  of  free 
acid  within  the  stomach  does  not  occur  until  from 
forty -five  minutes  to  an  hour  after  breakfast,  and 
from  one  to  two  hours  after  dinner.  These  results 
were  obtained  chiefly  by  the  use  of  methyanilin  violet 
and  tropseolin,  bodies  delicately  responsive,  by  color- 
change,  to  the  presence  of  free  acid.  There  is  little 
doubt  in  my  mind  that  hydrochloric  acid  is  devel- 
oped in  the  stomach  at  an  earlier  period  than  that 

1  Deutsch.     Archiv    Klin.     Med.,    xxiii.    369.       See    also 
Jahresb.  ii.  d.  Fortschr.  d.  Thier-Chemie,  1880,  p.  302,  and 
Danilewsky,  Centralb.  f.  d.  Med.  Wiss.,  1880. 

2  Zeitschr.  f.  Physio! .  Chemic,  iii.  205. 


36      Notes  from  the  Physiological  Laboratory 

above  indicated,  but  it  seems  very  probable  that  by 
immediate  combination  with  albuminoids  it  loses 
somewhat  of  its  characteristic  activity.  This  is  il- 
lustrated by  an  observation  made  in  the  course  of 
this  study,  namely,  that  the  addition  of  small 
amounts  of  potassium  iodide  to  dilute  solutions  of 
acid-albumen  containing  two-tenths  of  one  per  cent, 
of  hydrochloric  acid  does  not  result  in  the  libera- 
tion of  iodine.  The  addition  of  the  same  amount 
of  the  iodide  to  the  same  quantity  of  an  aqueous 
solution  of  hydrochloric  acid  of  the  same  degree 
of  acidity  results  in  an  immediate  liberation  of 
iodine. 

This  interesting  discovery  of  two  stages  of  acidity 
in  the  gastric  juice  has,  I  believe,  not  yet  been  in- 
corporated in  the  text-books.  It  serves  to  reconcile 
the  contradictory  opinions  so  frequently  found  as  to 
the  value  to  the  economy  of  saliva  as  a  digestive 
fluid,  and  explains  the  completely  diverse  results 
obtained .  by  such  careful  workers  as  Frerichs,1  and 
Bidder,  and  Schmidt.2 

Besides  an  observance  of  the  time-limitations  just 
indicated,  I  would  suggest  the  advisability  of  milk 

1  Wagner,  Handwoerterbuch.  d.  Physiologie,  iii.,  a,  772. 

2  Bidder  und  Schmidt,  Verdauung  u.  Stoffwcchsel,  p.  27. 


of  the   University  of  Pennsylvania.  37 

as  a  vehicle  for  the  administration  of  hydrobronaic 
acid.  The  curd  thus  formed  is  fine  and  flocculent, 
the  mixture  closely  resembling  buttermilk  in  taste 
and  appearance,  and  in  no  wise  suggesting  medicine. 
I  have  taken  as  much  as  a  tablespoon ful  of  the  di- 
lute acid  in  a  tumbler  of  milk  without  any  repug- 
nance. The  milk  used  must  be  raw.  With  this, 
as  with  most  other  acids,  boiled  milk  gives  tough 
and  bulky  coagula.1 

As  regards  the  exhibition  of  the  iodide  of  potas- 
sium, the  rationale  of  its  time  relations  is  altogether 
different.  Although  this  drug  is  distinctly  alkaline, 
its  presence  in  a  mixture  of  hydrated  starch  and 
saliva  certainly  does  not  suspend  the  action  of  the 
amylolytic  ferment,  nor,  so  far  as  I  can  determine, 
materially  retard  it.2  When,  however,  the  iodide  is 
added,  even  in  very  small  amount,  to  a  mixture  of 
artificial  gastric  juice  and  egg  albumen  or  fibrin,  the 
rapidity  of  peptone  formation,  as  determined  Jby  the 

1  Randolph :    Verbal    Communication   on   Differences   be- 
tween  Raw    and   Boiled    Milk.— Proc.    Acad.   Nat   Sci.    of 
Phila.,  1884,  p.  120. 

2  Langley  &  Eves,  Jour,  of  Physiology,  iv.,  p.  19,  have 
shown  that  although  a  distinctly  alkaline  medium  retards 
salivary  action,  the  presence  of  a  proteid  body  in  the  digest- 
ive mixture  will  prevent  this  retardation. 

4 


38     Notes  from  the  Physiological  Laboratory 

nascent  mercuric  iodide  reaction  *  or  by  the  biuret 
reaction  and  control  test,  is  greatly  diminished. 
This  result  is  not  due  to  a  slight  diminution  in  the 
acidity  of  the  solution,  caused  by  the  addition  of 
an  alkaline  body;  for  the  same  effect  is  noted  when 
the  acidity  of  the  solution  is  at  once  again  brought 
up  to  the  normal  degree.  The  pepsin  is  apparently 
but  little,  if  at  all,  affected  by  the  presence  of  the 
iodide,  if  we  may  judge  by  the  indifference  of 
ptyalin  to  the  drug,  and  by  the  fact  that  quantities 
of  the  iodide  corresponding  to  the  maximal  thera- 
peutic dose  neither  entirely  suspend  the  peptic  ac- 
tivity, nor  induce  greater  retardation  of  the  diges- 
tion than  do  much  smaller  quantities.  A  slight 
effect  is  exerted  by  the  iodide  upon  the  proteid 
food-stuffs,  evidenced  in  an  increased  toughness  pro- 
duced in,  e.g.,  fibrin,  and,  when  the  drug  is  abun- 
dantly present,  in  the  acquisition  by  the  albuminoid 
of  a  slightly  yellow  tinge,  due  to  staining  by  iodine, 
which  is  liberated  by  the  free  acid  of  the  artificial 
gastric  juice. 

The  most  important  factor  in  the  delay  of  pep- 
tonization  lies  in  the  power  possessed  by  potassium 

1  Kandolph :  A  Keaction    Common  to  Peptone  and  Bile- 
salts.—  Proe.  Acad.  Nat.  Sci.  of  Phila.,  1884. 


of  the   University  of  Pennsylvania.  39 

iodide,  even  in  relatively  minute  quantity,  of  pre- 
cipitating acid  albumen  in  solutions,  which  shall, 
after  its  addition,  possess  the  normal  degree  of 
acidity  of  human  or  even  canine  gastric  juice.  The 
same  may  be  said  of  potassium  bromide  and  of  sev- 
eral other  analogous  compounds.  The  precipitation 
effected  by  the  iodide  is  so  complete  that  when  solu- 
tions of  acid-albumen  are  thus  treated  and  filtered, 
the  still  acid  filtrate  yields  no  trace  of  proteid  mat- 
ter. This  observation,  which  is  doubtless  old, 
though  I  have  been  as  yet  unable  to  find  it  re- 
corded, tends  to  show  that  the  time  at  which  the 
administration  of  this  drug  is  least  liable  to  disturb 
digestion  is  either  during  or  immediately  after  the 
ingestion  of  food. 

There  are  several  t  sources  of  error  in  attempts  at 
deduction  from  the  results  of  artificial  digestion,  as 
ordinarily  performed.  Thus  the  continued  activity 
of  a  digestive  fluid  is  largely  conditioned  by  the  re- 
moval of  the  products  of  its  action  soon  after  their 
formation.  This  occurs  in  the  living  viscus,  but 
not  in  the  test-tube  of  the  experimenter.  The 
maintenance  of  the  normal  temperature  of  the  ac- 
tive stomach  is,  of  course,  readily  accomplished,  but 
the  conscientious  imitation  of  other  factors  in  the 
normal  digestive  process  implies  not  only  a  constant 


40     Notes  from  the  Physiological  Laboratory 

mechanical  intermingling  of  food-stuff  and  digestive 
fluid,  but  the  continued  addition  of  small  amounts 
of  the  digestive  fluid  itself.  I  have  nearly  perfected 
an  apparatus  which  in  a  large  degree  obviates  the 
difficulties  just  cited. 

In  it  artificial  salivary  digestions  are  conducted  in 
a  thin  tube  of  fish-bladder,  closed  at  one  end,  which 
is,  by  mechanical  means,  kept  in  gentle  agitation. 
The  contents  of  this  tube  are  maintained  at  the 
proper  temperature  by  a  surrounding  body  of  warm 
water  which  is  slowly  but  constantly  changed.  For 
gastric  digestions  the  animal  membrane  is  substi- 
tuted by  one  offering  equally  great  surface  for  dial- 
ysis, but  resistant  to  peptic  action.  Despite,  how- 
ever, the  inaccuracies  attending  existing  methods  of 
study,  the  following  deductions  from  the  facts,  old 
and  new,  which  are  here  presented,  appear  justi- 
fiable. 

I.  That    the    earliest    production    of    free    acid 
within  the  stomach  is  approximately  three-fourths 
of  an  hour  after  a  meal ;  its  appearance  being  still 
futher  delayed  by  the  ingestion   of  food   in    large 
quantity. 

II.  That  hydrobromic  acid   is   liable  to  impede 
the  digestion  of  starchy  foods   when  administered 
with  the  interval  just  named ;  and, 


of  the   University  of  Pennsylvania  41 

III.  That  iodide  of  potassium  should  be  given  at 
such  time  and  in  such  dilution  that  its  absorption 
shall  be  complete  before  the  appearance  of  free  acid 
within  the  gastric  contents.1 

1  Since  this  paper  was  read,  I  find  that  Landois  in  the  last 
edition  of  his  "  Lehrbuch  der  Physiologic,"  1885,  p.  306, 
accepts  without  question  the  results  of  Von  den  "Velden  and 
others  here  summarized.  The  same  authority  (p.  311)  quotes 
Fubini  and  Fiori  as  stating  that  potassium  iodide  impedes 
gastric  digestion.  Chambers,  in  his  "  Manual  of  Diet,"  Phila- 
delphia, 1875,  p.  257,  advises  that  potassium  iodide  be  admin- 
istered before  meals,  "  as  the  mixture  of  the  drug  with  food  in 
the  stomach  diminishes  the  efficiency  of  both." 


42     Notes  from  the  Physiological  Laboratory 


•VII. 

ON  THE   DIGESTION   OF  RAW   AND   OF 
BOILED   MILK. 

DK.  N.  A.  RANDOLPH  referred  to  certain  pro- 
found changes  produced  in  milk  by  boiling.  In 
this  operation  the  casein  is  not  coagulated,  but  there 
is  an  evolution  of  sulphuretted  hydrogen  (Schreiner), 
a  diminution  in  the  gaseous  constituents  of  the  fluid 
and  a  change  in  the  amount  of  ozone  present. 

The  most  striking  difference  between  raw  and 
boiled  milk  lay  in  their  respective  responses  to 
rennet  and  acids. 

At  the  body-temperature  the  firm  coagulation  of 
raw  milk  occurred  almost  immediately  upon  the 
addition  of  a  neutral  rennet  solution,  whereas  boiled 
milk,  under  the  same  conditions,  did  not  clot  for  a 
far  longer  period,  and  the  coagula  were  not  firm. 
On  the  other  hand,  dilute  or  strong  acids  were  ten- 
fold as  active  upon  boiled  as  upon  raw  milk.  Some 
time  after  making  these  experiments  Dr.  Randolph 
found  that  so  far  as  acids  and  rennet  were  con- 


•    of  the   University  of  Pennsylvania.  43 

cerned,  similar  results  had  been  obtained  by  Schreiner 
(Chem.  Centralbl.,  III.  Folge,  IX.  Jahrg.),  and  he 
desired  to  present  his  observations  in  these  particu- 
lars simply  as  confirmatory  of  those  of  that  observer. 
Artificial  digestions  showed  that  milk  was  more 
readily  digested  when  raw  than  when  boiled.  This 
was  further  confirmed  by  a  comparative  examina- 
tion and  weighing  (in  over  fifty  cases,  and  in  which 
he  was  aided  by  Dr.  Roussel)  of  the  contents  of  the 
stomach  after  raw  and  boiled  milk  had  been,  in 
different  individuals,  undergoing  actual  gastric  di- 
gestion. In  these  cases  the  residue  found  in  the 
stomachs  of  those  persons  receiving  boiled  milk  was 
greater  than  the  similar  residue  found  in  the  stomachs 
where  raw  milk  had  been  undergoing  digestion  for 
the  same  length  of  time.  [In  obtaining  the  gastric 
contents  of  the  individuals  under  observation,  tur- 
peth  mineral  was  used  in  the  first  series  of  eight 
persons  with  most  unsatisfactory  results.  It  was 
always  thereafter  substituted  by  hypodermic  injec- 
tions of  apomorphia.] 


44     Notes  from  the  Physiological  Laboratory 


A  STUDY  OF   THE   NUTRITIVE   VALUE   OF 
BRANNY   FOODS. 

FROM  an  economic  stand-point  the  question  of  the 
nutritive  value  of  bran  is  one  of  great  importance, 
for  the  removal  of  this  portion  of  the  wheat  implies 
a  loss  of  from  17  to  20  per  cent,  in  the  weight 
of  the  grain.  In  spite  of  this  loss,  which  neces- 
sarily renders  white  bread  more  expensive  than  that 
made  from  whole  wheat-flour,  even  the  poorest  in- 
habitants of  most  civilized  countries  where  bread  is 
not  the  staple  food,  insist  upon  eating  the  bread 
made  from  the  finer  grades  of  flour.  A  tendency 
so  widespread  as  this  would  apparently  indicate  the 
unconscious  summation  of  the  experiences  of  many 
generations,  and  go  far  toward  proving  the  pro- 
priety of  such  a  selection. 

The  use  of  flour  representing  the  entire  wheat- 
grain  has,  however,  been  long  and  ably  advocated ; 
the  reasons  given  for  the  retention  of  bran  being 
that  its  removal  entails  the  loss  of, — 


of  the   University  of  Pennsylvania.  45 

I.  "  Nutritive  salts"  (Niihrsalze  of  Liebig). 
II.  Carbohydrates. 

III.  Proteids,  notably  gluten. 

The  facts,  also,  that  branny  foods  in  common 
with  many  others  will  spur  an  atonic  bowel  to 
activity,  give  due  bulk  to  its  contents,  and  induce 
the  passage  of  stools  of  the  normal  or  feculent  con- 
sistency are  noteworthy,  but  their  further  consider- 
ation is  beyond  the  limits  of  the  present  paper. 
The  other  reasons  for  the  retention  of  bran  in  wheat- 
flour  will  be  discussed  seriatim. 

I.  The  fact  that  fine  flour  contains  a  much  smaller 
percentage  of  salts  than  does  either  bran  or  the  whole 
wheat — a  fact  evidenced  by  the  relatively  small 
amount  of  ash  which  it  yields — forms  the  basis  of 
the  theory  of  Liebig,1  that  in  the  removal  of  bran 
nutritive  salts  of  value  are  lost.  The  investigations 
of  Meyer 2  and  Forster 3  are  often  cited  as  showing 
that  after  the  removal  of  bran,  these  salts  are  still 
present  in  quantity  sufficient  for  the  needs  of  the 
economy. 

Our  experiments  upon  young  pigs,  described  fur- 
ther on,  show  that  although  survival  is  quite  pos- 

1  Chemische  Briefe,  1851. 

2  Zeitschrift  f.  Biologie,  vol.  vii.  p.  33. 

3  Ibid.,  vol.  ix.  pp.  293-380. 


46      Notes  from  the  Physiological  Laboratory 

sible  upon  an  exclusive  diet  of  bread  from  white 
flour,  growth  is  much  more  active  upon  a  diet  of 
bread  containing  a  greater  amount  of  inorganic 
matter.  It  is  possible  that  Liebig's  estimate  of  the 
needful  amount  of  inorganic  matters  was  too  high, 
but  it  is  equally  noteworthy  that  there  is  a  ten- 
dency on  the  part  of  late  writers  to  give  insufficient 
prominence  to  the  importance  of  these  elements  of 
food.  It  may  not  be  out  of  place  here  to  mention 
a  striking  illustration  of  the  absolute  necessity  for 
inorganic  salts  in  the  fluids  of  the  economy,  as  re- 
corded by  Dr.  S.  Ringer.1  This  observer  found 
that  while  minnows  were  kept  in  ordinary  tap  water 
they  would  live  for  weeks  unfed.  When,  however, 
they  were  placed  in  distilled  water  they  died  on  an 
average  in  four  hours  and  a  half.  Further,  that  in 
a  rude  imitation  of  spring  water,  made  by  the  ad- 
dition to  distilled  water  of  potassium  and  calcium 
chlorides,  and  of  sodium  bicarbonate,  the  fish  lived 
on  an  average  about  two  weeks.  Study  of  the  fac- 
tors in  the  experiments  showed  that  death  was  due 
to  a  diminution  of  salts  in  the  economy  of  the  fish. 
That  such  diminution,  even  when  very  slight,  could 

1  Journal  of  Physiology,  vol.  iv.  No.  vi.,  Feb.  1884,  in  the 
appended  Proc.  Physiol.  Soc.,  session  Dec.  13,  1883. 


of  the   University  of  Pennsylvania.  47 

result  fatally,  was  shown  by  an  analysis  of  the  dis- 
tilled water  after  the  death  of  the  fish ;  traces  only 
of  inorganic  matter  being  found. 

II.  The  loss  of  carbohydrates  involved  in  the 
removal  of  bran,  appears  at  first  sight  not  inconsid- 
erable, as  it  amounts  to  about  20  per  cent,  of  the 
carbohydrates  present  in  the  entire  grain.  The 
members  of  this  group  represented  in  bran  are 
starch  and  cellulose.  The  former  is  present  in  ex- 
tremely small  amount,  while  the  latter,  as  has  been 
proven  by  the  experiments  of  Bonders,1  Mulder,2 
and  Poggiale,3  is  digestible  in  any  noteworthy 
degree4  by  the  herbivora  only.  The  observer  last 
named  subjected  a  given  weight  of  dry  bran  to  the 
successive  actual  digestions  of  two  dogs  and  one  hen, 
and,  thereafter,  was  able  to  recover  over  65  per  cent, 
of  its  non-nitrogenous  constituents.  The  loss  in 
cellulose  was  probably  much  less  than  that  here  in- 
dicated, for  we  have  found  that  during  the  macera- 
tion of  bran  in  the  digestive  tract,  certain  portions 

1  Nederl,  Lancet,  vol.  vi.  pp.  227,  244. 

2  Physiologische  Chomic,  p.  1024. 

3  Comptes-Rondus,  vol.  xxxvii.  p.  173. 

4  See,  also,  Weiske  (Centralblatt,  No.  26,  1870),  who  finds 
that  a  small  percentage  of  cellulose,  especially  when  cooked, 
is  dissolved  in  the  human  digestive  tract. 


48      Notes  from  the  Physiological  Laboratory 

become  detached  from  the  main  flake,  and  are  with 
the  greatest  difficulty  recovered. 

III.  Wheat-bran  contains  a  considerable  but  vary- 
ing proportion  of  nitrogenous  compounds,  averaging, 
however,  about  14  per  cent.1  This  fact  has  per- 
mitted the  continued  existence  of  two  widely  cred- 
ited assumptions :  (a)  That  this  nitrogen  exists  in 
albuminoid  combination,  or,  in  other  words,  is  in  a 
nutritious  form ;  and  (6)  that  the  prote'id  matter  of 
wheat  is  contained  almost  exclusively  in  specific  cor- 
tical cells  of  the  grain, — the  so-called  "  glu ten-eel  Is." 

(a)  Nearly  all  the  existing  estimates  of  the  pro- 
portion of  proteids  in  food-stuffs  are  based  upon  the 
hypothesis  that  all  of  the  contained  nitrogen  is 
present  in  some  albuminoid  combination.  The  per- 
centage of  nitrogen  in  a  given  food  is  therefore  as- 
certained, multiplied  usually  by  either  6.5  (Pay en) 
or  6.33  (Ritthauseu)  and  the  result  recorded  as  the 
percentage  of  proteid  matter.  It  has  lately  been 

1  Dempwolf,  Ann.  d.  Chem.  u.  Pharm.,  vol.  cxl.  p.  343. 
His  figures,  of  interest  here,  are  as  follows  :  The  amount  of 
nitrogenous  matter  in  the  whole  wheat  was  14  35  per  cent. 
The  amount  varied  in  the  different  grades  of  white  flour  from 
11.01  to  15.56  per  cent.  The  nitrogenous  matter  of  the  two 
grades  of  bran  made  from  this  wheat  was  respectively  13.93 
and  14.06  per  cent. 


of  the  University  of  Pennsylvania.  49 

conclusively  proven  that  nitrogen  in  non-albuminoid 
combination — i.e.,  in  compounds  not  capable  of  afford- 
ing nourishment  to  any  of  the  higher  organisms — is 
present  in  many  food -stuffs,  and  especially  in  those 
of  vegetable  origin.  As  a  case  in  point  may  be 
mentioned  the  analysis  of  AVigner,1  in  which  it  is 
shown  that  of  the  total  nitrogenous  matter  of  the 
entire  wheat-grain,  87.9  per  cent,  is  coagulable, — 
i.e.,  distinctively  proteid.  Of  the  bran  only  42.4  per 
cent,  of  its  nitrogenous  compounds  are  coagulable, 
whereas,  in  the  flour,  89.7  per  cent,  of  these  bodies 
come  under  the  head  of  true  proteids.  Yet  more 
marked  instances  of  the  inaccuracies  attending  the 
ordinary  methods  of  estimating  proteids  have  be- 
come evident  in  the  course  of  researches  by  Schulze 
and  Barbieri,2  who  find  that  of  the  entire  nitrogen 
of  the  potato  but  56.2  per  cent,  enters  into  the  com- 
position of  albuminoid  matter,  while  in  the  fodder- 
beet  only  20  per  cent,  of  its  contained  nitrogen  is 
thus  combined,  the  remaining  80  per  cent,  aiding  in 
the  formation  of  amides,  nitrates,  and  ammonia.  It 
is  evident  from  these  facts  that  estimates  of  the  nu- 


1  Der  oeslerr.  ungar.  Miiller,  1879,  p.  52. 

2  Quoted  by  Voit,  Hermann's  Hdb.  d.  Physiol.,  vol.  vi.  p. 

462. 

5 


50      Notes  from  the  Physiological  Laboratory 

tritive  value  of  branny  and  other  foods,  based  upon 
the  percentage  of  nitrogen  present,  must  be  received 
with  caution. 

(6)  The  term  "gluten -cell"  is,  through  a  wide- 
spread misapprehension,  applied  to  the  cells  consti- 
tuting the  fourth  layer  (Parkes)  of  the  wheat-grain. 
These  cellular  elements  exist  usually  in  a  single 
stratum,  as  irregularly  cuboidal  bodies  in  each  of 
which,  surrounded  by  a  dense  and  laminated  cellu- 
lose wall,  is  seen  the  semi-opaque  granular  contents. 
Upon  the  addition  of  reagents,  especially  in  the  form 
of  caustic  alkaline  solutions,  there  is  almost  con- 
stantly noticeable  a  differentiation  of  the  contents 
strongly  suggesting  the  presence  of  a  nucleus. 
Under  these  conditions,  also,  a  coalescence  of  many 
of  the  individual  granules  forming  the  contents  oc- 
curs with  the  formation  of  several  highly  refractive 
spheroidal  bodies,  an  appearance  which  has  led 
Payen  (as  quoted  by  Dr.  Richardson)  to  use  the 
name  ole"if£res  as  a  synonyme  for  the  cellular  constit- 
uents of  the  fourth  coat.  The  hypothesis  that  the 
cells  of  this  layer  are  the  chief  gluten-bearers  of  the 
wheat-grain  is  usually  attributed  to  Donders.1  The 


1  Nederl,  Lancet,  iv.  739;  vi.  227,  244.     Third  series,  vol 
i.  377. 


of  the   University  of  Pennsylvania.  51 

return  of  bran  to  flour  was  at  about  the  same  period 
also  advocated  by  Millon  and  Mege  Mouries.1 

From  this  time  on,  with  but  few  dissenting  voices, 
the  "  gluten  -cell"  has  been  generally  spoken  of  as 
the  index  of  the  nutritive  nitrogenous  matter2  of  the 

1  Comptes-Kendus,  vol.  xliv.  p.  47. 

2  By  general  consent  the  albuminoids  of  the  wheat-grain  are 
grouped  together  as  gluten,  which  is>,  however,  further  sepa- 
rable into  gluten-fibrin,  gluten-casein,  gliadin,  and  mucedin, 
proteid  bodies  practically  equal  in  nutritive  value,  but  difler- 
ing  in  certain  physical  properties,  notably  that  of  solubility. 
It  must  therefore  be  borne  in  mind  that  in  all  methods  of 
separating  gluten  from  the  other  constituents  of  the  grain,  its 
(relatively  small)  soluble  portion  is  removed  with  the  starch, 
and  that  any  estimate  of  the  quantity  of  gluten  based  upon 
such  methods  will  probably  be  belo\v  rather  than  above  the 
actual   amount.     Kitthausen    (Die   Eiweiss-Korper  der   Ge- 
treidearten,  1872)   believes    that   a  certain   amount  of  true 
albumen  should  be  included  with  the  constituents  of  gluten 
just  mentioned.     An  observation  of  Denis  (^lemoire  sur  le 
sang,  1859)  confirmed  by  Hoppe-Seyler  (Med.  Chem.  Unters., 
1867)  and  Weyl  (Ber.  d.  deutsch.  Chem.  Ges.,  xiii.  10,  1880) 
demonstrates   that  a  portion  of  the  proteids  of   the  cereals 
exists  in  the  form  of    a  globulin.     Thus   the   observer  last 
named  has  shown  that  in  wheat-flour  trca'ted  with  a  15  per 
cent,   solution  of  sodium   chloride,  no   formation  of  gluten 
occurs.     We  have  found  that  bran,  when  macerated  in  15  per 
cent,  salt  solution,  yields  a  considerable  amount  of  proteid 
matter  precipitable  by  nitric  and  picric  acids.     "VVe  inclii.e 


52     Notes  from  the  Physiological  Laboratory 

wheat  grain,  while  the  central  portion  included 
within  this  layer,  and  constituting  fully  80  per  cent, 
of  the  grain,  has  been  popularly  regarded  as  being 
made  up  almost  exclusively  of  cellulose  and  starch, 
and  attempts  have  even  been  made  to  estimate  the 
nutritive  value  of  certain  cereal  food-stuffs  by  a 
microscopical  determination  of  the  proportion  of 
"  gluten-cells"  present.1 

The  manifest  impropriety  of  such  methods  has  of 
late  been  strongly  emphasized  by  Prof.  Richardson, 
of  this  city,  and  Prof.  Leeds,  of  Hoboken.  The 
credit  of  the  first  disproof  of  the  exclusive  limita- 
tion of  gluten  to  the  cells  of  the  fourth  layer  is 
probably  due  to  Schenk,2  who  treated  sections  of 
wheat-grain  with  Millon's  reagent,  a  pink  coloration 
of  the  endosperm  resulting.  This  coloration  was 
most  vivid  at  the  periphery,  indicating  a  gradual 
condensation  of  the  proteid  constituents  of  the  grain 
as  the  cortex  was  approached.  The  same  writer 
found  ."no  coloration  of  the  ' gluten-cells7  as  a 
result  of  this  reagent/7  an  observation  which  we 
cannot  confirm;  for,  apart  from  the  readily  demon- 

to  believe,  however,  that  this  is  not  a  true  albumen.  (See 
Vines,  Journal  of  Physiology,  vol.  iii.  p.  93.) 

1  E.  Cutter,  M.D  ,  Gaillard's  Med.  Journ.,  Jan.  1882. 

2  Anat.-Physiol.  Untersuch.,  p.  32,  Wien,  1872. 


of  the   University  of  Pennsylvania.  53 

strable  slight  coloration  of  the  contents  of  "gluten- 
cells"  after  the  application  of  Millon's  reagent,  it  is 
more  than  difficult  to  conceive  a  cell,  however  spe- 
cialized, which  shall  exhibit  no  proteid  matter  as  a 
portion  of  its  contents.  Schenk  also  noted  in  arti- 
ficial gastric  digestions  of  sections  of  wheat,  that 
the  starch-granules  which  (to  a  great  extent)  fill 
the  cells  of  the  central  portion  of  the  grain  became 
detached,  and  from  this  fact  deduced  the  just  propo- 
sition that  the  starch-granules  lay  imbedded  in  some 
albuminoid  substance.  In  a  study  of  the  distribu- 
tion of  gluten  within  the  wheat-grain,1  the  senior 
writer  has  described  several  methods  for  the  ocular 
demonstration  of  gluten,  in  very  considerable 
amount,  in  that  portion  of  the  grain  included 
within  the  fourth  layer,  and  entirely  independent  of 
the  "gluten-cells."  The  methods  were  as  follows: 

If  whole  wheat-grains  be  macerated  in  water,  to 
which  a  few  drops  of  ether  have  been  added  to  pre- 
vent germination,  they  will  in  a  few  days  become 
thoroughly  softened,  and  the  contents  of  each  grain 
may  then  be  squeezed  out  as  a  white,  tenacious  mass. 

Examination  of  the  remaining  bran  shows  the 

1  Randolph,  Tree.  Acad.  Nat.  Sci.,  Philadelphia,  Dec.  11, 
1883,  p.  308. 

5* 


54     Notes  from  the  Physiological  Laboratory 

"gluten-cells'7  undisturbed,  closely  adhering  to  the 
cortical  protective  layers. 

By  now  carefully  washing  the  white  extruded 
mass,  the  major  part  of  the  starch  may  he  removed; 
and,  upon  the  addition  of  a  drop  of  iodine  solution, 
microscopic  examination  shows  numerous  net-works 
of  fine  yellow  fibrils,  still  holding  entangled  in  their 
meshes  many  starch-granules,  colored  blue  by  the 
iodine. 

In  carefully  washed  specimens,  the  sponge-like 
net-works  are  seen  to  retain  the  outline  of  the  central 
starch-filled  cells,  and  evidently  constitute  the  pro- 
toplasmic matrix  in  which  the  starch -granules  lay. 
Upon  gently  teasing  such  a  specimen  under  a  mod- 
erate amplification,  the  fibrils  will  be  seen  to  become 
longer  and  thinner  in  a  manner  possible  only  to 
viscid  and  tenacious  substances, — a  class  represented 
in  wheat  by  gluten  alone. 

An  eminently  satisfactory  proof  of  the  proteid 
nature  of  these  central  net- works  may  be  obtained 
by  heating  the  specimen  in  the  solution  of  acid 
nitrate  of  mercury  (Millon's  reagent),  when  the 
fibrils  will  assume  the  bright  pink  tint  characteristic 
of  albuminoids  under  this  treatment.  The  results 
of  the  application  of  the  xanthoproteic  and  biuret 
reactions  are  equally  conclusive,  but  more  care  is 


of  the    University  of  Pennsylvania.  55 

required  in  the  use  of  these  proteid  tests,  aud  the 
resultant  differentiation  is  not  so  clear.  Reticuli, 
similar  to  those  above  described,  but  much  broken 
and  consequently  far  smaller,  may  be  seen  upon 
close  examination  scattered  through  fine  white  flour, 
without  the  use  of  any  reagent. 

In  even  the  thinnest  sections  of  the  wheat-grain, 
the  gluten  of  the  central  portion  is  always  masked 
by  large  numbers  of  starch -granules.  These  may 
to  a  large  extent  be  removed  by  immersing  the 
section  for  a  short  time  in  liquor  potassae,  with 
subsequent  careful  washing.  The  alkali  effects  the 
hydration  and  partial  solution  of  the  starch ;  but  if 
its  application  be  too  long  continued,  the  gluten  will 
also  be  dissolved.  This  treatment  is  well  adapted 
to  show  the  rather  dense  gluten  net-works  usually 
found  adherent  to  bran  immediately  below  the 
fourth  layer. 

The  most  satisfactory  method  of  studying  the 
distribution  of  gluten  in  sections  of  wheat  is  that 
of  artificial  salivary  digestion.  If  the  section  be 
gently  boiled  for  a  moment  to  hydrate,  the  starch 
then  transferred  when  cool  to  filtered  saliva,  and 
maintained  for  from  half  an  hour  to  an  hour  at  a 
temperature  of  about  98°  Fahr.,  all  the  starch  will 
be  dissolved,  while  the  insoluble  proteid  and  other 


56      Notes  from  the  Physiological  Laboratory 

constituents  will  remain  in  situ,  and  entirely  unal- 
tered. The  same  result  may  be  obtained  from  a 
somewhat  more  prolonged  digestion  of  the  unboiled 
section.  A  section  of  wheat-grain  thus  treated  will 
exhibit  throughout  its  entire  central  portion  close- 
meshed  gluten  net-works,  which  become  slightly 
denser  toward  the  cortex  of  the  grain.  The  pro- 
teid  character  of  these  reticuli  is  here,  as  in  the  first 
method,  susceptible  of  micro-chemical  demonstration. 
Upon  the  application  of  Millon's  reagent  to  such  a 
section,  a  relatively  very  faint  coloration,  indicating 
the  presence  of  albuminoids,  is  noticeable  in  the 
"gluten-cells,"  while  the  gradual  condensation  of 
the  gluten  of  the  endosperm,  as  the  fourth  layer  is 
approached,  is  evident  even  to  the  unaided  eye. 

The  fact  that  the  gluten  net-works  become  denser 
toward  the  periphery  of  the  endosperm,  together 
with  the  presence  of  non-albuminoid  nitrogenous 
compounds  in  the  perisperm,  explains  the  notable 
percentage  of  nitrogen  found  in  bran  as  ordinarily 
roughly  removed. 

The  small  proportion  of  albuminoids  present  in 
the  cells  of  the  fourth  layer  as  evidenced  by  their 
feeble  response  to  the  proteid  tests,  together  with 
the  very  considerable  quantity  of  gluten  which  we 
have  shown  to  exist  in  the  central  four-fifths  of  the 


of  the   University  of  Pennsylvania.  57 

grain  (i.e.,  the  portion  lying  within  the  fourth 
layer),  justifies  us  in  the  conclusion  that  by  far  the 
major  portion  of  the  nutritious  nitrogenous  matters 
exist  in  entire  independence  of  the  "gluten-cells." 

The  difficulties  which  attend  the  complete  isola- 
tion of  these  cells,  however,  have  as  yet  rendered 
impossible  any  accurate  estimation  of  the  proportion 
of  their  proteid  contents.  Admitting  for  the  mo- 
ment that  the  "gluten-cells"  contain  albuminoids  in 
any  noteworthy  amount,1  there  are  yet  present  con- 
ditions which  seriously  affect  if  they  do  not  entirely 
nullify  the  nutritive  efficiency  of  this  portion  of  the 
grain. 

The  first  of  these  conditions  is  the  presence  of  the 
rough  bran-scales,  which,  by  increasing  peristalsis, 
so  hasten  the  passage  of  the  entire  intestinal  con- 
tents that  complete  digestion  and  absorption  are  pre- 

1  Apart  from  the  statement  of  Schcnk,  above  cited,  the  en- 
tire absence  of  gluten  in  the  cells  of  the  fourth  layer  has  been 
latterly  affirmed  by  Mege  Mouries,  who  is  quoted  by  Payen 
(Substances  Alimentaires)  to  the  effect  that  these  cells  are 
"  filled  with  nitrogenous  substances,  of  which  gluten  is  not 
at  all  one."  He  finds  the  cells  in  question  to  contain,  in  ad- 
dition to  the  salts  of  magnesium,  lime,  and  p»tasb,  a  peculiar 
diastatic  ferment,  cereulin,  whose  function  is  the  transforma- 
tion of  the  starch  of  the  grain  into  dextrine  and  glucose  for 
the  nourishment  of  the  germinating  seed. 


58      Notes  from  the  Physiological  Laboratory 

vented.  The  second  is  that,  owing  to  the  dense  cel- 
lulose walls  of  the  "gluten-cells,"  their  contents  are 
practically  unaffected  by  the  digestive  juices.  The 
fact  that  the  presence  of  branny  scales  in  the  diges- 
tive tract  prevents  the  thorough  digestion  of  the  in- 
testinal contents,  and  induces  the  passage  of  faeces 
containing  a  considerable  excess  of  undigested  nitro- 
genous matter,  is  fully  attested  by  the  observations 
of  Meyer  and  Rubner.1  Edward  Smith2  has  also 
closely  studied  the  economic  phase  of  this  subject, 
and  reports  most  unfavorably  upon  the  use  of 
branny  foods,  stating  that  the  diminished  absorption 
of  nutritive  matters,  entailed  by  their  use,  more  than 
counterbalances  the  (apparent)  gain  in  cheapness. 
Of  interest  in  this  connection  is  the  observation  of 
Fr.  Hofmann,3  who  noted  that  the  amount  of  fa3ces 
passed  upon  a  meat  diet  was  remarkably  increased 
by  the  addition  of  cellulose  to  the  food  taken. 

The  feeble  response  of  the  "gluten-cell"  to  re- 
agents and  digestive  juices  has  been  noted  by  several 
observers.  Thus  Bonders4  states  that  these  bodies 
are  digested  by  the  herbivora,  but  not  by  dogs  or 

1  Zeitschrift  f.  Biologie,  vol.  vii.,  ibid.,  xix.  1883,  p.  46. 

2  "Foods,"  1875,  p.  175. 

3  Yoit,  Sitzgsber.  d  bayr.  Acad.,  Dec.  18G9. 
*  Physiologic  (German  ed.),  p.  273. 


of  the   University  of  Pennsylvania.  59 

man.  Similar  results  are  recorded  by  Poggiale,1 
and  for  domestic  fowls  by  Meissner  and  Fliige.2  J. 
Lehmann3  records  the  feeding  of  pigs  for  thirty- 
two  days  on  bran  which  contained  almost  no  flour, 
with  a  nearly  negative  gain  in  weight,  although 
the  bran  contained  15.5  per  cent,  of  nitrogenous 
matters. 

The  ability  of  herbivora  to  digest  "gluten-cells" 
and  similar  bodies  is  probably  due  to  the  relatively 
powerful  amylolytic  ferments  of  their  digestive  fluids, 
for  it  has  been  demonstrated  that  pepsin  is  unable  to 
traverse  cellulose.4  It  has  also  been  shown  by  one 
of  us5  that  the  cells  of  the  fourth  layer  are,  to  all 
appearance,  entirely  unaffected  by  prolonged  artifi- 
cial digestions, — salivary,  gastric,  and  pancreatic, — 
and  further  that  their  contents  were  but  little 
changed,  and  their  walls  in  nowise  disintegrated 
by  immersion  for  some  days  in  strong  acids  and 
alkalies. 


1  Comptes-Rendus,  1853. 

2  Zeitsch.  f.  rat.  Med.,  vol.  xxxi.  p.  185,  and  vol.  xxxvi.  p. 
184. 

3  Amtsbl.  f.  d.  Handl.  u.  wer.  d.  K5nigr.  Sacbsen,   1868, 
No.  2. 

4  Hammersten,  Jabresber.  d.  Tbierchemie,  vol.  iii.  p.  207. 

5  Randolph,  Proc.  Acad.  Xat.  Sciences,  1883,  p.  311. 


60     Notes  from  the  Physiological  Laboratory 

Lately,  however,  in  the  course  of  an  admirable 
paper  upon  the  nutritive  relations  of  gluten,  Rubner1 
has  stated  that,  although  branny  foods  increase  the 
amount  of  nitrogen  in  the  faeces,  fully  three-fourths 
of  the  nitrogenous  matter  of  bran  is  digested.  In 
the  bran  used  there  was  present  4  per  cent,  of  nitro- 
gen, "equalling  25  per  cent,  albuminoids,"  while 
in  the  bran  obtained  from  the  faeces  of  the  persons 
tinder  observation  only  0.9  per  cent,  of  nitrogen  was 
obtainable.  We  hesitate  in  criticising  the  results  of 
so  able  an  observer,  but  it  seems  to  us  that  there 
were  two  sources  of  error  in  this  portion  of  his 
investigation.  In  the  digestion  of  bran  the  free, 
adherent  gluten,  which  properly  belongs  to  the  more 
central  layers,  is,  of  course,  readily  dissolved,  with  a 
consequent  reduction  in  the  nitrogen  of  the  bran. 
Apart  from  this,  however,  a  loss  in  nitrogen  is  to  be 
expected,  from  the  diffusion  of  nitrogenous  crystal- 
loids. Further,  the  "gluten-cells"  become  so  sepa- 
rated from  the  true  bran,  during  their  maceration  in 
the  intestinal  contents,  that  it  is  nearly,  if  not  quite, 
impossible  to  recover  them. 

In  order  to  satisfy  ourselves  regarding  the  diges- 
tibility of  the  cells   of  the  fourth  coat,  we  have 

1  Zeitscb.  f.  Biologie,  vol.  xix.  1883,  p.  46. 


of  the   University  of  Pennsylvania.  61 

subjected   bran  with  its  adherent  "gluten-cells"  to 
actual  digestion  by  twelve  well-nourished  adults,  six 
males  and  six  females.     These  twelve  persons  were 
selected   from   a   larger   number   by  excluding   all 
whose  fseces  exhibited  under  microscopic  examina- 
tion any  inefficiency  in  the  amylolytic  and  proteo- 
lytic  digestive  ferments  as  evidenced  by  the  presence 
of  starch  or  muscle  fibre  in  more  than  a  minimal 
amount.     Sources  of  error  arising  from  individual 
peculiarities  having  been  eliminated  by  the  number 
of  persons  under  observation,  and  the  best  conditions 
for  digestion  having  been  obtained,  these  persons 
then  received  daily  for  three  days,  in  addition  to 
their  regular  food,  one  ounce  of  thoroughly  boiled 
bran.     Their  fasces  for   the  last  two   days  of  the 
treatment  were  submitted  to  close  microscopical  ex- 
amination, with  results  so  nearly  uniform  as  not  to 
require  tabulation.     In   every  case  the  number  of 
"gluten-cells'7  present  was  more  than  sufficient  to 
render  a  diagnosis  of  the  food  taken  a  matter  of 
great  ease.     In  two-thirds  of  the  cases  no  evidences 
of  disintegration  of  any  of  the  cells  could  be  found 
upon  repeated  examination  of  many  fields  from  each 
specimen.     In  four  cases  a  small   proportion  (less 
than  10  per  cent.)  of  the  numerous  cells  examined 
showed  evidences  of  having  been  affected   by  the 

G 


62      Notes  from  the  Physiological  Laboratory 

digestive  process,  the  cell  contents  having  become 
lighter  in  color  and  less  opaque.  If,  however,  any 
true  digestion  of  the  cells  had  occurred,  it  is  evident 
that  many  of  these  elements  in  different  stages  of 
disintegration  would  have  been  seen. 

As  a  rule,  we  found  that  the  several  layers  of  the 
bran  presented  an  appearance  not  of  having  been 
digested,  but  simply  of  having  been  subjected  to 
prolonged  maceration.  Thus  the  three  coats  of  the 
true  bran  while  entirely  unchanged  were  frequently 
found  separated  from  each  other.  We  had  expected 
to  find  the  fourth  layer  closely  adherent  to  the  third, 
as  is  the  case  in  dry  bran,  but  in  the  majority  of 
specimens  these  two  coats  became  separated,  and 
occasionally  large  sheets  of  "gluten-cells,"  to  all 
appearance  perfectly  normal,  were  seen.  As  a  rule, 
however,  that  portion  of  the  faecal  mass  representing 
the  meal  at  which  bran  was  taken1  was  found  to 
contain  these  thick-walled  cells  in  nearly  every 
field. 

1  We  did  not  find  it  needful  to  give  with  the  bran  any  col- 
oring matter  to  differentiate  in  the  fasces  the  meal  at  which  it 
was  taken,  as  the  scales  of  bran  were  always  a  sufficient  in- 
dex. "When  requisite,  such  differentiation  may  readily  be 
obtained  by  the  method  of  Cramer  (Zeitschr.  f.  Physiol. 
Chem.,  vol.  vi.  p.  354),  or  that  of  Kubner  (1.  c.). 


of  the   University  of  Pennsylvania.  63 

A  study  of  the  nutritive  relations  of  a  given  food 
may  be  approached  from  three  sides:  First,  from 
that  of  the  exact  chemical  composition  of  the  food, 
a  knowledge  absolutely  essential  to  any  scientific 
scheme  of  diet.  Second,  from  that  of  the  various 
excretions  of  the  individual  or  animal  upon  the 
diet  in  question ;  and,  third,  from  the  more  clinical 
stand-point  of  study  of  the  effects  exerted  by  a  given 
diet  upon  the  growth  and  nutritive  processes  of  the 
organism  under  observation.  After  an  examination 
of  branny  food  in  the  light  of  the  first  two  methods, 
we  attempted  its  study  by  the  third.  To  this  end 
six  young  pigs  of  the  same  litter,  and  all  in  fair 
health,  were  weighed  and  placed  under  the  same 
conditions  in  pairs  in  three  separate  bins.  Those  in 
the  first  bin  daily  received  bread  especially  made 
from  whole  wheat-flour,  in  amount  corresponding  to 
one-fourth  pound  of  dry  bread  each.  To  those  in 
the  second  bin  was  given  a  corresponding  amount  of 
bread  made  from  wheat  whose  three  external  coats 
only  had  been  removed.  The  pigs  in  the  third 
bin  received  the  best  white  bread  in  amount  cor- 
responding to  the  standard  above  mentioned.  A 
sufficient  (fixed)  quantity  of  water  was  given  twice 
daily.  The  following  table  shows  the  weight  of 
eacli  pair  at  the  beginning  of  the  observation,  and 


64      Notes  from  the  Physiological  Laboratory 


at  the  end  of  respectively  ten  and  thirty-two  days 
thereafter : 


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>-» 

!-S 

1-5 

^ 

•-S 

Weeks. 

Lb». 

Lbs. 

ZA«. 

its. 

£&«. 

I. 

6 

Broad  from  whole  wheat. 

24.5 

29.0 

4.5 

:«.25 

8.75 

II. 

6 

("Brown  luvad  from  de-) 
|    corticated  wheat  j 

24.75 

28.25 

3.5 

34.50 

975 

III. 

6 

White  bread  

25.25 

27.25 

2.0 

33.0 

7.75 

Comparison  of  these  weights  exhibits  curious  and 
apparently  contradictory  results,  viz.,  that  during 
the  first  ten  days  the  gain  was  greatest  in  the  pigs 
fed  upon  whole  wheat  bread,  whereas  at  the  end  of 
thirty-two  days  of  such  feeding  the  gain  was  most 
pronounced  in  the  pigs  fed  upon  bread  made  from 
wheat  whose  three  outer  coats  had  been  removed. 
The  cause  of  this  variation  in  results  is  not  far  to 
seek.  At  the  commencement  of  the  experiments 
the  animals  were  small,  and  the  food  given  was  in 
each  case  more  than  sufficient  to  replace  the  waste 
in  both  the  tissues  and  circulatory  fluids.  Even  the 
pair  fed  upon  bread  containing  the  innutritious  and 
waste-inducing  bran,  digested  and  absorbed  suffi- 
cient proteid  matter  to  supply  the  needs  of  the 
tissues,  and  normal  growth  was  also  favored  by  the 


of  the   University  of  Pennsylvania.  65 

presence  of  a  bulky  intestinal  contents  of  a  mechan- 
ically stimulating  nature,  and  also  by  the  nutritive 
salts  which  were  present  in  this  bread  in  larger 
amounts  than  in  others.  On  the  other  hand,  at  the 
end  of  the  thirty-two  days  the  animals  had  notably 
increased  in  size;  the  food  given  was  then  barely 
sufficient  for  the  needs  of  the  economy,  and  any 
conditions  impeding  its  complete  digestion  and  ab- 
sorption produced  a  notable  effect  upon  the  rate  of 
growth  of  these  young  animals. 

It  must  be  borne  in  mind  that  these  experiments 
relate  only  to  the  value  of  the  different  breads  when 
taken  alone  to  the  exclusion  of  other  foods.  The 
experiments  of  Rubner  before  cited  leave  no  doubt 
that  a  white  bread  contains  more  assimilable  nutri- 
ment than  does  one  made  from  the  whole  wheat, 
but  this  does  not  render  it  a  desirable  food-stuff  for 
exclusive  use.  On  the  contrary,  a  weaned,  but  still 
quite  young  omnivorous  mammal  thrives  better 
upon  an  exclusive  diet  of  bran  bread  than  on  white, 
and,  presumably,  because  the  earthy  and  alkaline 
salts  are  present  in  greater  abundance  in  the  former, 
and,  also,  because  the  indigestible  constituents  tend 
to  give  to  the  intestinal  contents  that  bulk  and  con- 
sistence which  are  essential  to  the  hygiene  of  the 

digestive  tract.     But,  as  has  been  shown  by  Edward 
6* 


66      Notes  from  the  Physiological  Laboratory 

Smith  and  others,  the  branny  scales  are  needlessly 
irritating,  and  unduly  hasten  the  passage  of  food1 
but  partially  digested  and  absorbed.  The  end  which 
popular  hygiene  attempts  to  effect  by  the  retention 
of  bran  in  breadstuff's  can  be  better  attained  by  other 
means.  Thus  the  nutritive  salts  of  food  so  fre- 
quently lost  in  ordinary  methods  of  preparation  are 
readily  restored  by  the  concentration  of  the  liquor 
in  which  meats  and  vegetables  are  cooked  into  a 
soup  stock,  as  is  practised  in  almost  every  French 
kitchen.  Again,  the  various  fresh  green  vegetables 
used  as  salads  yield  in  abundance  these  inorganic 
food-stuffs,  the  presence  of  which  we  have  seen  is 
indispensable  to  normal  tissue  activity.  A  further 
advantage  of  these  and  other  .succulent  vegetables 
lies  in  the  fact  that  their  cellulose,  while  efficient  in 
giving  proper  bulk  and  consistence  to  the  stools,  is, 
as  compared  with  bran-scales,  soft  and  unirritating 
to  the  digestive  tract. 

From  the  facts,  old  and  new,  which  have  been 

1  An  observation  worthy  of  mention  in  this  connection  is 
that  of  Kubner,  who  finds  that  while  the  presence  of  much 
woody  fibre  and  harder  cellulose  in  the  intestinal  contents 
induces  the  passage  of  stools  containing  an  excess  of  undi- 
gested proteid  foods,  the  absorption  of  fats  under  the  same 
conditions  is  not  materially  affected. 


of  the   University  of  Pennsylvania.  67 

presented,  the   following   deductions   appear  to  us 
justifiable: 

I.  The   carbohydrates  of  bran   are   digested   by 
man  to  but  a  slight  degree. 

II.  The  nutritive  salts  of  the  wheat-grain    are 
contained  chiefly  in  the  bran,  and,  therefore,  when 
bread   is   eaten   to   the    exclusion  of    other   foods, 
the  kinds  of   bread   which  contain  these  elements 
are   the    more   valuable.      When,   however,   as   is 
usually  the   case,  bread  is  used  as  an  adjunct  to 
other  foods  which  contain  the  inorganic  nutritive 
elements,  a  white  bread  offers,  weight  for  weight, 
more  available  food  than  does  one  containing  bran. 

III.  That  by  far  the  major  portion  of  the  gluten 
of  wheat   exists   in   the  central  four-fifths   of  the 
grain,  entirely  independent  of  the  cells  of  the  fourth 
bran-layer  (the  so-called  "gluten-cells").     Further, 
that  the  cells  last  named,  even  when  thoroughly 
cooked,   are   little   if    at   all    affected    by   passage 
through  the  digestive  tract  of  the  healthy  adult. 

IV.  That  in  an  ordinary  mixed  diet  the  reten- 
tion of  bran  in  flour  is  a  false  economy,  as  its  pres- 
ence so  quickens   peristaltic   action   as  to   prevent 
the  complete  digestion  and  absorption  not  only  of 
the  proteids  present  in  the  branny  food,  but  also  of 
other  food-stuffs  ingested  at  the  same  time;  and, 


68      Notes  from  the  Physiological  Laboratory 

V.  That  inasmuch  as  in  the  bran  of  wheat  as  or- 
dinarily roughly  removed  there  is  adherent  a  note- 
worthy amount  of  the  true  gluten  of  the  endosperm, 
any  process  which  in  the  production  of  wheaten 
flour  should  remove  simply  the  three  cortical  pro- 
tective layers  of  the  grain  would  yield  a  flour  at 
once  cheaper  and  more  nutritious  than  that  ordi- 
narily used. 


of  the   University  of  Pennsylvania.  69 


IX. 

A  METASTATIC   HEAT  REGULATOR. 

THE  instrument  about  to  be  described  is  adaptefl 
to  maintain  a  constant  temperature  within  any  water- 
or  air-chamber  heated  by  gas,  the  degree  of  temper- 
ature thus  maintained  being  adjustable  at  will. 

Reference  to  the  illustration  shows  an  air-ther- 
mometer so  modified  that  the  rise  of  mercury  in  the 
limb  B  will  cut  off  the  gas-supply  which  passes 
through  its  bifurcated  extremity.  A  second  modifi- 
cation lies  in  the  accurately-fitting  glass  stop-cock 
D,  connected  with  the  air-chamber  A.  By  means 
of  this  stop-cock  the  tension  of  the  air  within  the 
chamber,  and  consequently  the  height  of  the  mer- 
cury in  the  tube  B,  is  readily  adjustable.  It  is  evi- 
dent that  when  the  mercury  is  forced  high  up  in  B, 
a  relatively  slight  increase  in  the  temperature  of  the 
surrounding  medium  will  be  sufficient  to  so  expand 
the  air  in  A  as  to  force  the  column  of  mercury  to» 
the  point  of  shut-off.  On  the  other  hand,  a  far 
higher  temperature  will  be  needed  to  effect  the 


70     Notes  from  the  Physiological  Laboratory 

shut-off  when  the  columns  of  mercury  in  A  and 
B  are  of  the  same  height.  In  practice  the  adjust- 
ment is  effected  by  placing  the  instrument  in  a  me- 
dium of  the  required  temperature,  the  cock  D  is 
opened,  and  air  slowly  forced  in  with  a  syringe, 
until  the  mercurial  column  in  B  is  nearly  at  the 
point  of  bifurcation ;  the  precise  height  varying,  of 
course,  with  the  dimensions  of  the  instrument,  and 
being  readily  ascertained  by  practice. 

The  pressure  of  the  gas  employed  must  be  kept 
quite  low,  otherwise,  as  the  mercury  rises  above  the 
point  of  bifurcation,  a  portion  will  be  blown  out. 
One  of  the  simpler  gas-pressure  regulators  may  be 
advantageously  inserted  between  the  source  of  gas- 
supply  and  the  heat  regulator.  It  is  wrell  also 
that  the  diameter  of  the  limb  C  should  be  some- 
what greater  than  that  of  its  fellow,  and  also  that 
its  point  of  junction  with  B  should  be  somewhat 
constricted  in  order  that  a  smaller  variation  in  tem- 
perature shall  effect  either  the  patency  or  occlusion 
of  the  gas  exit. 

When  the  mercury  rises  in  B  a  trifle  beyond  the 
point  of  bifurcation,  the  passage  of  gas  from  G  to 
E  is  arrested,  and  the  flame  from  the  burner  I  is 
at  once  extinguished.  Were  no  further  provision 
made,  the  vessel  and  its  contents  would  soon  cool 


of  the   University  of  Pennsylvania.  71 

sufficiently  to  again  permit  the  flow  of  gas,  which 
would  then  pass  off,  unburnt,  through  I.  This  dif- 
ficulty is  obviated  by  the  use  of  a  second  gas-jet,  J, 


so  placed  as  to  re-light  the  burner  I,  upon  the  re- 
newed passage  of  gas,  and  so  minute  as  not  to  give 
out  sufficient  heat  to  counterbalance  that  which  is 
lost  from  the  vessel  by  radiation,  etc.,  during  the 


72     Notes  from  the  Physiological  Laboratory 

temporary  stoppage  in  the  main  jet.  This  second- 
ary jet  may  be  readily  made  from  a  common  brass 
blow-pipe,  bent  in  the  form  shown  in  J,  and 
steadily  supported  in  such  manner  tjiat  its  little 
flame  may  constantly  play  immediately  above  the 
opening  of  the  main  burner.  It  is  usually  neces- 
sary to  still  further  reduce  the  small  opening  of  the 
blow-pipe  by  squeezing  it  with  pliers,  or  by  other 
means.  The  secondary  flame  is  fed  by  a  branch,  H, 
from  the  source  of  gas-supply. 

The  instrument  must  be  protected  from  touching 
the  base  of  the  containing  vessel  either  by  suspen- 
sion or  by  the  intervention  of  a  plate  of  cork  or 
other  non-conductor.  It  must  also  be  held  steadily 
vertical,  and  should  always  be  accompanied  by  a 
thermometer  to  verify  its  adjustment.  It  is  also 
well  to  have  each  of  the  exposed  surfaces  of  mer- 
cury covered  by  a  drop  or  two  of  glycerine  to  pre- 
vent oxidation. 


of  the   University  of  Pennsylvania.  73 


x. 


ON    THE    BEHAVIOR    OF    PETROLATUM    IN 
THE  DIGESTIVE  TRACT. 

THE  mixture  of  hydrocarbons,  recognized  by  the 
pharmacist  under  the  name  of  petrolatum,  and  pop- 
ularly used  under  the  commercial  names  of  cosmo- 
line  or  vaseline,  presents,  on  superficial  inspection, 
few  points  of  difference  from  some  of  the  organic 
fats  of  the  same  consistency.  Close  examination  re- 
veals differences,  both  in  physical  properties  and  in 
chemical  constitution,  between  the  bodies  just  com- 
pared. One  point  of  difference,  which  I  have  as  yet 
been  unable  to  find  recorded,  lies  in  the  respective 
behavior  of  these  two  groups  when  in  contact  with 
the  absorbent  surfaces  of  the  digestive  tract.  Tims, 
while  the  organic  fats,  as  ordinarily  taken  in  food, 
are  readily  and  almost  completely  absorbed,  this  soft 
paraffine  is  entirely  rejected,  and  found  unchanged 
in  the  faeces. 

During  eight  days  I  took,  daily,  one-half  ounce 

7 


74      Notes  from  the  Physiological  Laboratory 

of  commercial  vaseline,  in  addition  to  my  regular 
diet.  Digestion  was  in  nowise  altered,  and  no  ap- 
preciable results  ensued.  Later,  two  healthy  adults 
each  received,  in  the  course  of  forty-eight  hours,  one 
ounce  of  vaseline.  Their  alvine  dejections  for  three 
days  from  the  beginning  of  this  observation  were 
collected  and  dried,  and,  at  the  suggestion  of  Dr. 
John  Marshall,  of  the  University  of  Pennsylvania, 
extracted  with  petroleum  ether.  Making  a  slight 
allowance  for  incompleteness  in  extraction,  the  vase- 
line ingested  was,  in  each  case,  recovered  in  its  to- 
tality, showing* that  it  had  passed  through  the  econ- 
omy unchanged  and  unabsorbed. 

There  are  some  important  medical  applications  of 
these  facts,  the  discussion  of  which  would  be  out  of 
place  here,  and  which  I  reserve  for  further  experi- 
ment;1 but  the  following  deductions  appear  permis- 
sible, and  are  of  strictly  biological  interest : 

I.  Pure  petrolatum,  while  entirely  unirritating  to 
the  digestive  tract,  is  valueless  as  a  food-stuff. 

II.  The  results  of  the  experiments  here  described 
lend  support  to  the  theory  that  oleaginous  matters 

1  The  chief  medical  use  of  these  facts  lies  in  the  adminis- 
tration of  vaseline  as  a  bland  emollient  to  the  intestinal  sur- 
face. I  have  in  several  individuals  succeeded  in  checking 
diarrhoeas  of  irritation  by  this  simple  means. 


of  the   University  of  Pennsylvania.  75 

are  dependent  for  their  absorption,  not  upon  mechan- 
ical, but  upon  vital  activities,  and  that  in  such  ab- 
sorption the  selective  power  of  the  protoplasm  of  the 
intestinal  epithelium  is  manifested. 


76     Notes  from  the  Physiological  Laboratory 


XI. 


CUTANEOUS  ABSORPTION  OF  NICOTINE. 

DR.  N.  A.  KANDOLPH  described  the  results  of  a 
series  of  experiments  performed  by  Mr.  Samuel  G. 
Dixon  and  himself,  relative  to  the  absorption  of 
nicotine  by  the  uninjured,  healthy  skin  of  the  liv- 
ing rabbit.  In  these  experiments  only  rabbits  of 
ascertained  good  health  were  used.  The  fur  of  the 
abdomen  was  carefully  clipped  (not  shaved);  suffi- 
cient time,  usually  seven  days,  being  allowed  to  in- 
tervene between  this  operation  and  the  application 
of  the  drug  to  the  skin,  thus  permitting  any  slight 
scratch  made  at  this  time  to  fully  heal.  The  absence 
of  cutaneous  lesion  was  further  confirmed  by  close 
examination  under  a  strong  hand-magnifier.  The 
drug  was  then  applied  to  the  skin,  no  friction  being 
used.  In  order  to  preclude  the  possibility  of  its 
vaporization  and  subsequent  absorption  by  the  lung- 
surface,  the  nicotine  was  placed  upon  an  adhesive 
plaster,  the  backing  of  which  was  made  of  sheet- 
rubber.  The  plaster,  with  the  drug  in  its  centre, 


of  the  University  of  Pennsylvania.  77 

was  then  applied  in  the  open  air,  on  a  windy  day. 
Different  doses  were  applied ;  thus,  in  one  case,  one 
drop  of  nicotine,  applied  to  the  skin,  caused  death  in 
five  hours  and  eleven  minutes.  In  each  of  three 
cases  a  similar  application  of  ten  drops  was  fatal  in 
respectively  one  hundred  and  nine  minutes,  twenty- 
eight  minutes,  and  thirty-six  minutes.  In  the  fifth 
case,  a  similar  application  of  fifteen  drops  of  nicotine 
caused  death  in  twenty-eight  minutes. 

Of  the  ante-mortem  symptoms,  contraction  of  the 
pupil  was  constant,  and  often  appeared  very  quickly. 
Other  prominent  symptoms  were  great  trembling, 
with  subsequent  loss  of  muscular  power  in  the 
extremities.  In  one  case  actual  convulsions  were 
noted,  and  in  others,  coldness  of  the  skin  and  in- 
creased lachrymal  and  nasal  secretion.  Immedi- 
ately upon  the  death  of  two  of  the  animals  (after 
the  ten-  and  fifteen-drop  doses  respectively)  blood 
was  removed,  defibrinated,  and  tested  with  mercuric 
chloride  for  the  presence  of  nicotine  in  the  manner 
detailed  by  Wormley  (Micro-Chemistry  of  Poisons). 
In  each  of  these  two  instances  characteristic  groups 
of  crystals  were  found  upon  microscopic  examination 
of  the  extract  from  the  blood. 


78      Notes  from  the  Physiological  Laboratory 


XII. 

ON   THE   DIETETIC  FACTOR  IN  THE  TREAT- 
MENT  OF  ANGINA  PECTORIS. 

THERE  has  recently  been  under  my  care  a  patient 
suffering  from  true  angina,  in  whom,  as  is  not  seldom 
the  case,  any  slight  gastric  irritation  constituted  the 
immediate  exciting  cause  of  the  frequently-recurrent 
paroxysms. 

After  the  last  attack  there  existed  an  inability  to 
retain  the  lightest  and  simplest  foods,  their  ingestion 
inducing  not  only  nausea,  but  much  cardiac  distress. 
Eecourse  was  had,  with  advantage,  to  milk,  par- 
tially digested  by  the  commercial  Extractum  Pan- 
creatis ;  but  the  flavor  of  the  resultant  preparation 
was  unappetizing,  and  finally  became  repulsive  to 
the  patient,  who  whimsically  described  its  taste  as 
that  of  "  stewed  corpse." 

To  meet  this  emergency,  there  were  devised  two 
food  products,  which  I  have  not  seen  described,  and 
which,  in  practice,  proved  eminently  satisfactory. 

1.  Pancrcatized  Oysters. — The  oysters  of  an  or- 


of  the   University  of  Pennsylvania.  79 

dinary  stew  (containiDg  milk)  are  removed  and 
finely  minced,  then  returned  to  the  liquid  portion 
of  the  stew.  The  whole  is  brought  to  a  temperature 
of  100°  F.,  the  appropriate  proportions  of  pancreatic 
extract  and  sodium  bicarbonate  are  added,  and  the 
mixture  maintained  at  the  temperature  mentioned 
for  thirty  minutes,  with  occasional  stirring.  It  is 
then  strained  and  served,  and  forms  not  only  a 
highly  nutritious  and  palatable  soup,  but  one  which 
is  retained  by  very  irritable  stomachs,  and  utilized 
with  a  minimum  of  digestive  power.  After  boiling, 
to  prevent  the  further  action  of  the  digestive  fer- 
ment, gelatine  may  be  added,  and  the  mixture  served 
cold  as  a  jelly.  Cooked  tomato,  onion,  celery,  or 
other  flavoring  suited  to  the  individual  taste  of  the 
patient,  may  be  added  at  the  beginning  of  the  arti- 
ficial digestion,  and  the  solid  residue  removed  in  the 
final  process  of  straining,  at  which  time  it  will  be 
noticed  that  the  minced  oysters  originally  added 
have  been  in  great  part  dissolved. 

2.  Pancreatized  Milk-toast. — Ordinary  milk-toast, 
in  which  there  is  an  abundance  of  milk,  when 
digested  in  the  manner  just  described,"  becomes  an 
almost  homogeneous  pulpy  mass,  which,  when  the 
crusts  have  been  removed,  is  usually  acceptably 
retained  by  the  irritable  stomach.  In  extreme  cases, 


80     Notes  from  the  Physiological  Laboratory 

however,  it  may  advantageously  be  strained  and  the 
fluid  portion  alone  used,  in  which  the  partially  pep- 
tonized  solution  of  casein  of  the  milk  is  reinforced  by 
actually  digested  gluten  and  starch  of  the  bread, 
together  with  a  very  little  dextrin.  Plain,  light 
sponge-cake  may  be  similarly  digested,  and  occasion- 
ally forms  a  desirable  change. 

In  conclusion,  I  would  express  the  hope  that 
these  rather  homely  suggestions  may  prove  of  value 
in  other  hands,  in  extending  the  somewhat  scanty 
bill  of  fare  suited  to  patients  suffering  from  gastric 
hypersesthesia,  and  the  various  neurotic  troubles  of 
which  such  a  condition  may  be  the  exciting  cause. 


of  the   University  of  Pennsylvania.  81 


XIII. 

A   PAINLESS  ESCHAROTIC. 

IN  view  of  the  rapidly  growing  literature  of 
cocaine  it  is  not  impossible  that  the  application 
which  we  here  briefly  describe  has  already  been 
employed ;  but,  if  so,  it  has  escaped  our  scrutiny 
of  the  later  developments  regarding  this  drug. 

When  a  saturated  solution  of  cocaine  hydrochlo- 
rate  in  strong  nitric  acid  is  applied  to  the  uninjured 
skin,  the  ultimate  result  is  precisely  that  which 
would  occur  upon  the  similar  application  of  pure 
nitric  acid,  but  the  time  required  for  the  formation 
of  a  deep  eschar  is  considerably  longer  in  the  former 
than  in  the  latter  case. 

We  have  experimented  with  the  mixture  just 
mentioned  upon  several  individuals,  ourselves  in- 
cluded, and  can  safely  say  that  the  sensations 
attending  its  application  cannot  be  accurately  de- 
scribed as  painful.  There  is,  however,  a  slight 
pricking  sensation  soon  after  the  mixture  is  first 
dropped  upon  the  skin. 


82      Notes' from  the  Physiological  Laboratory 

Upon  one  person  a  control-experiment  was  insti- 
tuted in  the  following  manner:  Upon  his  right  arm 
were  placed  four  drops  of  strong  nitric  acid,  while 
upon  the  same  point  on  his  left  arm  was  similarly 
disposed  the'sarne  quantity  of  the  mixture  of  nitric 
acid  and  cocaine  hydrochlorate.  The  pure  acid 
caused  great  pain,  and  was  speedily  removed ;  the 
mixture,  which  was  applied  later,  caused  a  sensation 
described  as  "tickling,  with  slight  pricking,"  which 
soon  passed  away. 

In  two  cases  the  burned  points  were  covered  with 
absorbent  cotton  wet  with  a  two  per  cent,  solution 
of  cocaine  salicylate,  a  salt  which  we  have  not  yet 
seen  described,  but  which,  in  addition  to  the  pecu- 
liar properties  of  its  contained  alkaloid,  appears  to 
be  somewhat  antiseptic.  There  has  been  no  discom- 
fort after  the  formation  of  the  eschar.  Prof.  Harri- 
son Allen,  to  whom  we  presented  a  portion  of  our 
solution  of  the  salt  last  mentioned,  kindly  reports 
that  he  has  applied  it  several  times  in  his  practice 
as  a  substitute  for  other  salts  of  cocaine,  with  good 
results. 


of  the   University  of  Pennsylvania.  83 


XIV. 

A  NOTE  ON  THE  CUTANEOUS  ABSORPTION 
OF  SALICYLIC  ACID. 

Ix  view  of  the  fact  that  the  internal  administra- 
tion of  salicylic  acid  and  its  salts  is  not  infrequently 
capable  of  producing  or  increasing  gastric  irrita- 
bility, the  advantages  of  inducing  its  cutaneous  ab- 
sorption are  at  once  apparent.  By  the  application 
to  the  uninjured  skin  of  salicylic  acid,  rubbed  up  in 
a  thin  paste  with  olive  oil,  we  have  been  able  to 
demonstrate  the  presence  of  the  drug  in  the  urine  in 
each  of  seven  cases  in  which  such  application  was 
made.  In  six  of  these  cases,  an  existing  rheumatic 
attack  was  relieved  by  the  application.  Of  these,  in 
one  case  only  did  the  application  give  a  negative 
result. 

CASE  I. — Man,  set.  30,  of  rheumatic  habit,  who 
had  been  suffering  for  three  days  from  rheumatic 
pains  and  stiffness  in  the  right  thigh.  The  pain  had 
grown  daily  worse,  until  motion  of  the  limb  became 


84      Notes  from  the  Physiological  Laboratory 

almost  unbearable.  He  was  ordered  to  remain  in 
bed,  and  twenty  grains  of  salicylic  acid  were  rubbed 
into  a  paste  with  olive  oil,  and  gently  smeared  in 
each  axilla.  Four  hours  thereafter,  the  patient  felt 
somewhat  better;  and  the  urine  examined  at  this 
time  showed  the  presence  of  the  drug  upon  the  ap- 
plication of  the  ferric  chloride  test.  At  noon,  on 
the  following  day,  the  patient  reported  himself  as 
entirely  well. 

CASE  II. — Female,  set.  60,  suffering  from  fre- 
quently-recurrent and  severe  rheumatic  pains  in  the 
shoulder.  The  method  of  treatment  used  in  the 
preceding  case  was  here  employed,  and  the  patient 
reported  marked  relief  on  the  following  day,  at 
which  time,  also,  the  drug  was  found  in  her  urine. 

CASE  III. — Female,  set.  28.  Rheumatic  pains 
in  arm  and  shoulder.  Application  as  in  previous 
cases.  The  drug  here  proved  a  decided  irritant  to 
the  very  sensitive  skin,  and  was  removed  in  some 
fifteen  hours.  Results  negative.  Urine  not  exam- 
ined. Pain  and  stiffness  subsequently  disappeared 
after  the  exhibition  of  large  doses  of  sodium  sali- 
cylate  internally. 

CASE  IV. — Male,  set.  25,  frequently  subject  to 
rheumatism  in  the  left  shoulder,  and  always  re- 
lieved by  the  internal  use  of  sodium  salicylate ;  was 


of  ike   University  of  Pennsylvania.  85 

relieved  during  a  similar  attack  by  the  method 
already  described. 

CASE  V. — Male,  at.  34,  suffering  with  severe 
rheumatic  pains  in  left  shoulder. 

Thirty  grains  of  salicylic  acid  were  rubbed  up  in 
olive  oil,  gently  smeared  upon  the  left  side  of  the 
abdomen,  and  covered  with  rubber-cloth.  Here,  as 
in  the  other  cases,  the  urine  was  tested  for  the  drug 
in  question  at  the  time  that  the  application  was 
made,  with  negative  results.  Urine  passed  in  one 
hour  and  ten  minutes  thereafter  gave,  upon  the  ap- 
plication of  the  ferric  chloride  test,  the  response 
characteristic  of  the  presence  of  salicylic  acid ;  and 
this  reaction  was  observed  in  several  samples  of 
urine  from  this  patient  up  to  the  thirty-sixth  hour 
after  the  application  was  made.  In  twelve  hours 
the  rheumatic  symptoms  were  greatly  relieved,  and 
they  entirely  disappeared  within  twenty-four  hours. 

CASE  VI.1— Dr.  F.,  set.  29.  Rheumatic  swell- 
ing of  right  knee,  the  circumference  of  which  was 
one-third  greater  than  that  of  its  fellow.  Patient 
gave  history  of  previous  persistent  rheumatic  at- 


1  We  are  indebted  for  the  report  of  this  case  to  the  cour- 
tesy of  Dr.  William  Gray,  who  pursued  the  method  indi- 
cated at  our  suggestion. 


86      Notes  from  the  Physiological  Laboratory 

tacks.  Salicylic  acid  and  oil  (3ij  to  fSj)  were 
spread  upon  absorbent  cotton,  and  the  whole  gently 
wrapped  around  the  knee,  which  was  here  too 
acutely  sensitive  to  permit  of  any  friction.  No 
internal  medication  was  used.  In  twenty-four 
hours  there  was  marked  reduction  both  of  pain 
and  swelling,  and  within  three  days  the  patient  had 
entirely  recovered.  During  the  treatment,  swelling 
commenced  in  the  knee  of  the  opposite  side,  but 
disappeared  under  the  same  local  treatment  pursued 
with  the  joint  first  affected.  The  urine  was  several 
times  examined  during  the  treatment,  and  salicylic 
acid  found  therein. 

This  case  is  of  especial  interest  as  indicating  that, 
superadded  to  the  constitutional  impress  of  the 
drug,  there  was  a  specific  local  effect  at  the  place 
of  its  application. 

We  do  not  consider  that  the  results  of  the  six 
experiments  here  cited  would  warrant  us  in  an  un- 
qualified commendation  of  this  method  of  exhibit- 
ing salicylic  acid,  but  we  feel  fully  justified  in 
suggesting  that  a  fair  trial  be  given  it  by  the 
medical  profession. 

[The  following  brief  statements  summarize  the 
results  of  some  of  our  experiments  upon  Cutaneous 
Absorption,  which  are  as  yet  unpublished. 


of  the   University  of  Pennsylvania.  87 

In  general,  drugs  in  solution  in  oil  (not  oleates) 
are  absorbed  by  the  normal  human  skin  with  greater 
or  less  ease.  On  the  other  hand,  drugs  in  aqueous 
solution  are  not  so  absorbed.  Thus  we  have  shown 
that  salicylic  acid  in  oil  is  absorbed  by  the  healthy 
skin,  whereas  in  the  similar  application  of  salicylate 
of  sodium,  which  is  practically  insoluble  in  oil,  we 
have  never  been  able  to  obtain  evidence  of  cutane- 
ous absorption. 

In  this  connection  may  be  mentioned  the  fact, 
which  we  believe  has  not  hitherto  been  recorded, 
that  methyl  salicylate  (true  oil  of  wintergreen)  is 
apparently  absorbed  by  the  human  skin.  If  this 
oil  be  gently  rubbed  over  the  arm,  the  presence  of 
salicylic  acid  in  the  urine  is  readily  demonstrable  at 
the  end  of  an  hour  after  the  application.  We  say 
apparently  absorbed,  because  the  salicylate  in  ques- 
tion is  volatile,  and  consequently  may  be  absorbed 
by  the  lung  surface.  A  series  of  control  experi- 
ments was  instituted  to  determine  this  point.  A 
little  pledget  of  cotton,  saturated  with  oil  of  winter- 
green,  was  suspended  immediately  beneath  the  nos- 
trils in  such  wise  that  it  did  not  come  in  contact 
with  the  skin.  The  urine,  which  was  found  to  be 
free  from  salicylic  acid  at  the  beginning  of  the  ex- 
periments, constantly  showed  the  presence  of  this 


88      Notes  from  the  Physiological  Laboratory. 

drug  in  from  forty  to  fifty  minutes  thereafter.  The 
possibility  exists  that  the  specific  therapeutic  impress 
of  salicylic  acid  may  be  obtained  by  inhaling  an 
atmosphere  impregnated  with  this  volatile  salicylate. 
We  hope  to  report  upon  this  point  in  the  near  future. 
The  obstacles  which  prevent  the  cutaneous  absorp- 
tion of  drugs  in  aqueous  solution  are  the  resistant 
epiderm,  and,  much  more  important,  the  secretion  of 
the  sebaceous  glands.  A  very  simple  and  efficacious 
method  which  we  have  devised  for  removing  these 
obstacles  consists  in  the  addition  of  a  proteolytic 
ferment  to  the  solution  of  the  drug  used.  Thus 
trypsin  (prepared  by  Kiihne's  method)  is  added  to 
a  strong  solution  of  (e.g.)  morphia.  Absorbent  cot- 
ton is  saturated  with  the  mixture,  placed  upon  the 
skin,  and  covered  over  with  waterproof  plaster. 
The  natural  warmth  of  the  part  induces  the  activity 
of  the  ferment  and  the  consequent  solution  of  the 
epiderrn,  narcosis  supervening  in  from  one  to  two 
hours.  This  method,  when  applied  under  the  super- 
vision of  the  physician,  affords  one  advantage  over 
ordinary  modes  of  medication,  namely,  that  when 
the  desired  therapeutic  effect'is  obtained,  the  further 
absorption  of  the  drug  may  be  prevented  by  at  once 
removing  the  external  application.] 


